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Can sertraline cause weight gain: Does Taking Zoloft Cause Weight Gain?

Do antidepressants really cause weight gain?

In around a quarter of cases, long-term use of antidepressants is associated with a weight gain of 10 lb or more. For those who are already feeling less than stellar, this can be demoralising, fuelling anxieties about their health or appearance.

As Dr Derek Tracy of the Royal College of Psychiatrists explains, it is very normal to be concerned about weight gain.

“Few people will refuse to take medication because of this, but it will sometimes influence conversations about which particular medication to take,” he says. “Doctors should be responsive to these concerns, and mindful of potentially replacing one problem with another one. This is particularly important for some people – for example, if there is a history of type 2 diabetes or heart disease.”

Why weight gain happens

While gaining weight on antidepressants is far from inevitable (it all depends on how your body responds to that particular medication), it would be remiss to ignore the possibility.

In one recent large study, involving nearly 300,000 people, people who had used an antidepressant for more than a year were found to be at higher risk of weight gain. Compared to the control group, they were 21% more likely to put on weight, although there was a lot of variability in which drugs had which effect.

Studies of this kind can’t tell us why the weight gain happened, or even prove a causal relationship between antidepressants and weight gain. However, there are several theories as to why it might occur.

“Most antidepressants are effective through modulating the brain chemicals serotonin or noradrenaline; however, they can also unintentionally bind with other biochemical pathways in the brain and body, causing side effects,” says Tracy. “We think that when weight gain occurs, some of this is due to binding with the ‘histamine’ system in the brain.”

The older types of antidepressants (tricyclics) and the medication mirtazapine appear more likely to cause weight gain for this reason. Other types of antidepressants may have different effects on appetite and metabolism. And there are probably genetic factors determining your individual propensity towards weight gain.

Other factors

In some cases, there is a simpler explanation – you lost your appetite while depressed, and have regained it now you’re feeling better. This could be a positive thing, especially if you were underweight to begin with.

“Some weight gain can actually be an indirect sign of some recovery, if their mood is lifting and their appetite is returning to previous levels,” says Tracy.

Alternatively, your depression might be associated with overeating or low energy levels. These symptoms might persist for a while even once you’ve started antidepressants.

“People vary, and while it is more common for people to lose their appetite and eat less when depressed, we recognise that there is a group of people who will eat more at this time. This is sometimes worsened by a lack of activity and exercise in depression,” says Tracy.

Finding the right antidepressant

Most people, however, will not pile on the pounds on antidepressants. Unlike antipsychotics, which do carry a substantial risk of weight gain, antidepressants typically only have a modest impact. On balance, you might think that it’s worth gaining a few pounds for the sake of feeling better.

If your weight does seem to be spiralling upwards, solving the problem might be as simple as switching up your medication. For instance, venlafaxine, duloxetine and sertraline may be less likely to lead to weight gain than some other types of antidepressants. And while bupropion (also known as Wellbutrin) is not commonly prescribed in the UK, it is actually associated with modest weight loss.

“Anyone with concerns about weight gain should absolutely raise them with their doctor, and discuss if there might be more suitable specific medications for them and their physical and mental health,” says Tracy.

This is particularly important if you have a history of eating disorders or are already overweight. Antidepressants are not a one-size-fits-all medication, and it’s worth persisting until you find something that suits your individual needs.

Of course, even where there is some weight gain, it’s important to offset this against the benefits. Depression can be a debilitating condition and, if you’re suffering, you deserve to receive proper treatment.

On top of that, if you’ve been struggling to get out of bed, antidepressants may well give you the boost you need to start exercising and eating more healthily. Chances are, this will improve your mood still further and help bring your weight under control, creating a kind of virtuous circle.

“We must remember the cost of not treating depression itself,” says Tracy. “This can be worse for the body as well as the mind, including making it more difficult to exercise, be active and maintain a healthy lifestyle.”

Weight gain differs with various antidepressants

By Ronnie Cohen

NEW YORK (Reuters Health) – People who take antidepressants tend to put on a few pounds, a new study confirms, and some of the drugs are linked to more weight gain than others.

Using health records from one New England healthcare system, researchers studied 19,244 adults treated with antidepressants, recording their weights over the course of a year.

The results showed that people taking citalopram (Celexa), a selective serotonin reuptake inhibitor (SSRI), gained more than two and a half pounds, on average.

Other SSRIs were associated with weight gain similar to citalopram, with people taking fluoxetine (Prozac) gaining on average a pound and a half and those taking sertraline (Zoloft) gaining nearly two pounds, according to a report online June 4 in JAMA Psychiatry.

On the other hand, people taking bupropion (Wellbutrin) lost on average nearly half a pound. The tricyclic antidepressants nortriptyline and amitriptyline were also linked with significantly less weight gain than the SSRIs.

“Our study provides more support for the idea that if weight is a major concern, Wellbutrin is a good option,” senior author Dr. Roy Perlis told Reuters Health. Perlis is a psychiatrist at Harvard Medical School and director of the Center for Experimental Drugs and Diagnostics at Massachusetts General Hospital in Boston.

“There’s no question we see less weight gain with Wellbutrin,” he said. “But in absolute terms, the difference is rather small.”

On average, people taking antidepressants “will gain a very modest amount of weight . . . between half a pound and perhaps two pounds if they stayed on the medicine for about a year,” he said. But some people will gain much more, he said.

“We in practice have long since watched the effect of antidepressants on weight,” Dr. Anne Peters told Reuters Health. “The key to this medicine is don’t overmedicate; don’t use drugs unless there’s a good reason.”

Peters directs the University of Southern California Clinical Diabetes Program in Beverly Hills and was not involved in the current study.

In addition to depression, a substantial percentage of study participants were taking antidepressants for anxiety or pain or as an aid to quit smoking. People who take antidepressants for reasons other than depression and are prone to weight gain may want to consider alternatives, Peters said.

“We’ve got to individualize this and not keep people on antidepressants forever,” she said. “People shouldn’t stay on these drugs if they’re contributing to their weight gain and they’re no longer needed.”

On the other hand, she said, “Nobody wants to gain weight, but I sure don’t want to see people depressed.”

More than 60% of Americans taking antidepressants have been on them for two years or longer, and 14% have taken the drugs for 10 years or more, according to the CDC.

Peters noted that Wellbutrin can agitate anxious people and therefore may be a poor match for some people with depression.

Wellbutrin affects different brain chemicals than do SSRIs, and some of those chemicals may play a role in appetite. Researchers don’t know all the reasons why some antidepressants appear to cause weight gain and others do not, Perlis said.

Some people gain weight and others lose weight as a result of depression. Consequently, researchers have trouble untangling the effects of medication and the effects of depression on weight, Perlis said.

The new study also can’t prove the antidepressants were responsible for weight gain.

“A one-size-fits-all solution isn’t right,” Perlis said. “We desperately need newer, better antidepressants in terms of effectiveness.”

Perlis and one of his co-authors have consulted for and received funding from numerous antidepressant drug manufacturers. But Perlis said all the drugs he studied are now available as generics.

SOURCE: http://bit.ly/1p2CpwS

JAMA Psychiatry 2014.

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A Psychiatrist Explains Why Antidepressants Can Cause Weight Gain

There’s still a lot we don’t know about antidepressants and what they do to the body and the brain, but some side effects are widely known, including a dip in sex drive, and perhaps most commonly, weight gain.

While each individual’s experience of a medication might be unique, psychiatrist and mental health educator Dr. Tracey Marks breaks down the scientifically accepted reasons why antidepressants, mood stabilizers and anti-psychotic can sometimes lead people to put on weight.

While usually associated with the immune system and allergic reactions in the body, Marks explains that histamine works differently in the brain. h2 receptors play a role in the sleep wake cycle, maintaining body temperature, regulating endocrine, pain, cognition, and appetite.

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Blocking h2 receptors affects the satiety center, i.e. the part of the brain that makes you feel full. “People can have terrible carbohydrate cravings on some of these medications,” says Marks. “But it’s not enough to say ‘just don’t overeat’, because when you tamper with your ability to feel full, you don’t see your eating as stuffing down extra food. You’re eating because you’re still hungry, and you don’t feel satisfied.”

Marks notes that another side effect of blocking h2 receptors is a decrease in thermogenesis, the process of creating heat in the body by burning fat. This leads to a longer term, slower increase in weight. “When you burn less fat, it accumulates,” she says. “The more fat you have, the higher your BMI.”

Some anti-psychotic medications also block the 5HT2C receptors, a type of serotonin receptor in the brain. “It’s been shown in mice that if you activate the 5HT2C receptors, they lose weight because they eat less, and if you block the receptor, they become obese,” says Marks.

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Several studies into the side effects of drugs only report minimal weight gain, but Marks points out that these are often 12-week studies which neglect to account for the “creeping-up effect” of longer term weight gain due to histamine blocking.

There are things people can do to manage their weight when taking antidepressants. The simplest approach is to have a very strict diet and do plenty of intense exercise, such as resistance training, to build muscle and combat the slowed fat-burning process. Marks also lists several medication options which may help to mitigate weight gain — but these depend on your diagnosis and your current medication, and should be discussed with your doctor.

Philip Ellis
Philip Ellis is a freelance writer and journalist from the United Kingdom covering pop culture, relationships and LGBTQ+ issues.

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My Antidepressants Made Me Gain 20 Pounds—And I Was Shamed For It

I was home for Passover, sitting in my parents’ office—whenever I come back to New York, I always sneak in some financial guidance from my father. I was feeling especially accomplished, and just as I was getting up to celebrate my responsibleness with my parents’ rescue dog, my dad announced there was “one more thing.” He handed me a Post-it with illegible scrawl on it and asked me to read the note aloud. After a moment of deciphering, I managed to make out “125 to 135.” He announced that this was the healthy weight for my age and height and that he was pretty sure I was over it.

Before everyone starts hating on my dad for body shaming me in my family home, let me provide a little more context. I have been on and off antidepressants since I was four years old. I’ve had moderate to severe OCD pretty much my entire life, along with ever-present anxiety and bursts of depression. There have been times where I’ve needed medication and times when I’ve managed without. (“Managed” being the operative word—not to be mistaken for “flourished” or “excelled.”)

It did not feel good to feel unattractive. But it felt a hell of a lot better than wanting to die.

Although the medications have changed throughout the years, the one unfortunate constant is the side effects. These vary from sweatiness to sleepiness to—you guessed it—weight gain. Sometimes these effects aren’t immediately obvious. I spent four rather formative years (8–12) thinking I had a bad metabolism and would spend my life overweight. But the moment I got off Paxil, the pounds floated away and I was suddenly skinny. At the time, no one had realized my chunkiness was a medical side effect. Now, almost 17 years later, my family is well aware. So Dad intervened in his own special way and urged me to change medications.

Gaining excess weight as a medical side effect is not fun. Before I went on Zoloft last year, I was around 120 pounds. That day in the office, after my dad made me get on a scale, I weighed over 140, which is a significant difference on my 5’3” frame. I’m not oblivious; I knew I had gained weight. Many of the viewers on my YouTube channel had pointed it out. It was also impossible to ignore Instagram comments like “What happened to Allison” and “Damn, she really let herself go.” It did not feel good to feel unattractive. But it felt a hell of a lot better than wanting to die.

Please note: Being overweight is, of course, not inherently unattractive. But like most of us, I grew up in a society where skinny = pretty, and this is a hard notion to shake. It’s especially hard when your appearance is tied to your career, and complete strangers feel the need to comment on any noticeable change. I had spent so many years trying to change myself on the inside that it was exhausting to now feel pressure to do the same on the outside.

A little more context. One year before what I now refer to as the “Post-it incident,” I went through a devastating break-up. Romantic relationships have always been my biggest trigger, and this one knocked me out. Part of the problem was that I hadn’t been taking care of my mental health; as a result I lost my then boyfriend and any ability to function happily. It was the hair that broke my brain’s back, if you will. The night he left me I cried uncontrollably and announced/screamed my desire to no longer live. My mother flew out to California the next day for a “light suicide watch.” I’ve never tried to kill myself, but that’s due to familial obligation more than a lack of desire, so she probably figured it was better to be safe than sorry.

Within days, I had returned to a psychiatrist’s office for the first time in seven years and was back on medication for the first time since I was 21. For almost my entire twenties, I had been resisting meds because I was convinced I could “therapize” myself. This may have been the biggest mistake of my adult life. My OCD affected so many things. In addition to endlessly obsessing about finding the right partner, I fretted constantly about cleanliness. I spent most of my twenties unable to comfortably sit on friends’ couches for fear of contamination. I lived in a constant state of panic about things most people rarely even notice: When was the last time she washed that jacket? I have to make sure I pick up my suitcase without it touching my legs. Please, please, please don’t put your purse on my furniture. Will I be alone forever?

Okay, maybe a lot of people think about that last one. But I think about it a lot. I would get so anxious about my relationships that I ruined them.

And then came Zoloft. For the first time, maybe ever, I experienced what a balanced brain feels like. I had been on medication in the past, but combined with talk therapy and the healthy thought processes I’d been working on, this time it worked even better. I felt unbelievable relief. Who cared if I gained a few pounds in the process?

Unfortunately, a lot of people cared—including my family. Suddenly, I was faced with a choice: Should I risk upsetting a very precarious good thing by changing my medication or continue to live with a body I no longer recognized? For many months, the answer was obvious. My mental health was more important. I ignored the mean comments and told my parents to stop badgering me. It helped that I had started a new relationship with a boyfriend who was completely supportive and constantly assured me he was still attracted to my new frame. I felt proud that I was prioritizing my mental health over my vanity.

Because let me be clear: I am very vain. I obsess about my looks as much as anyone. I spend way too much money on eyelash extensions, and I’ve tried pretty much every overpriced hair product out there. I’m also on camera quite a bit, and there are hours of footage from my pre-medication days where I look like a different person. It would be a lie to say I haven’t masochistically re-watched quite a few on them recently, over and over again.

Suddenly my brain was filled with one of my oldest friends: self-hate.

So at a certain point, I broke. I couldn’t keep ignoring the number on the scale or the reflection in the mirror that I no longer recognized. The mean comments didn’t roll off my back anymore and my parents’ concern became my concern. Suddenly my brain was filled with one of my oldest friends: self-hate. I avoided my reflection and internally yelled at myself for looking disgusting. I felt like all the progress I’d been making toward loving myself was being overshadowed by this devilish side effect.

A week or so after the Post-it, I went back to my psychiatrist and asked to change medications. She put me on a newer drug, Trintellix, which has fewer side effects, and paired it with Wellbutrin, which is known to combat weight gain. I slowly started to wean off Zoloft under her supervision. (Quick PSA: NEVER change meds without medical supervision.) It wasn’t fun, and it wasn’t easy. I had multiple brain zaps and felt off for weeks. (Full disclosure: I went off caffeine at the exact same time, due to bad judgement and possible masochism.)

It’s hard to say exactly when I started feeling better with the new combination of meds, because I was going through an incredibly stressful time and yet another break-up. (Isn’t dating fun?!) But at a certain point, I felt the same level of stable on the Trintellix/Wellbutrin as I felt on the Zoloft. Six months later, I’ve lost ten of the twenty-plus pounds and I’m trying not to eat too many carbs. (Turns out it’s a lot harder to lose weight when you’re 29 than when you’re 12.)

Mental health should, without a doubt, always be a priority. For almost a year, the weight gain didn’t bother me. But then, all the external pressure created even more stress, so with the help of a doctor, I looked for a new option that would take everything into account. And despite the rollercoaster of side effects, I am still a huge proponent of medication. I don’t think I could have survived without it when I was younger, and I no longer feel like I’m “just surviving” with it now. I’m able to enjoy life in a way I couldn’t without chemical assistance.

I urge everyone suffering from anxiety, depression, OCD, or any other type of mental illness to seek professional help and treat their symptoms the same way they would treat a physical ailment: with proper care and medication. Do not let the fear of side effects get in the way of getting help. Because I can assure you, even when I was feeling my lowest about my body it was nowhere near as low as I felt the day my ex left me.

As for me now? My new medications are working, I’m slowly losing weight, and I’m sweatier than ever. But I can definitely live (well) with that.

If you or someone you know is struggling with suicidal thoughts, you can call the U.S. National Suicide Prevention Lifeline at 800-273-TALK (8255) or chat online.

Allison Raskin
Allison Raskin
Allison Raskin is a New York Times bestselling author and co-creator of the YouTube comedy channel, Just Between Us, which she shares with her best friend and comedy partner, Gaby Dunn.

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What is Selective Serotonin Reuptake Inhibitors (SSRI) Antidepressants?

SSRI Sexual Dysfunction

Sexual side effects are the most frequent antidepressant side effect reported by primary care patients.   In a study involving 2,163 adults who had undergone at least eight weeks of treatment with antidepressants, 79% showed some degree of sexual dysfunction. Dysfunction varies from decreased libido to inability to obtain orgasm, and erectile difficulty.

In both men and women, antidepressant-induced sexual side effects largely result from increased serotonin (5-HT) neurotransmission via reuptake blockade of serotonin transporters. Antidepressants that primarily increase dopamine and norepinephrine neurotransmission produce markedly fewer sexual side effects.

This provides the rationale for treatment using bupropion and other agents that simultaneously increase norepinephrine and dopamine signaling. It also suggests the theoretical basis for developing novel antidepressants that increase 5-HT and dopamine signaling. These findings are clinically relevant for patients who develop sexual side effects. And also attain substantial clinical improvement or remission of depression with serotonergic agents.

Serotonergic antidepressants produce the highest rates of sexual side effects.

Other mechanisms

Other possible mechanisms for SSRI sexual side effects include decreased dopaminergic transmission, cholinergic and alpha-adrenergic blockade. And inhibition of nitric oxide synthase 1, and prolactin elevation.

The American Psychiatric Association recommends we need to ask men and women whether sexual side effects are occurring with these medications.

Sexual dysfunction is under-reported if it is not specifically examined by clinicians. Because patients will not report sexual side effects due to embarrassment or perhaps due to lack of recognition of those symptoms as medication-related.

The association between major depressive disorder and sexual dysfunction is bidirectional. Moreover, estimated prevalence rates of antidepressant-induced sexual side effects are very high for several antidepressants. But the estimation of true prevalence is complicated by the high prevalence of sexual dysfunction in all patients. With mood disorders and by the under-reporting of sexual side effects.

Baseline sexual functioning should be assessed with validated rating scales at the same time depression is evaluated.

Should you blame your meds?

In the fifth part of our month-long “Take It Off Today” series, we look at medicines that can make you fat. It’s an unfortunate side effect, but some drugs can slow down your metabolism and increase your appetite. Madelyn Fernstrom, a show contributor and director of the Weight Management Center at the University of Pittsburgh Medical Center, was invited on “Today” to discuss what to do if you suspect that your medicine is making you fat.

Patients who start taking new medications may notice that they’re putting on a few extra pounds. Many blame the weight gain on their drugs. They may be right — or they may be wrong. All medications have some side effects or what is called the “risk-benefit ratio.” The truth is that weight gain is a common side effect for some drugs, but not all. Some patients may not realize that they have either changed their lifestyle or cut back on their physical activities.

So before you blame your medication for making you fat, determine if your weight gain is truly a side effect. Some drugs cause a slow, steady weight gain over a period of time; others can cause you to put on a couple pounds in a week. Here are some questions to ask yourself if you think your drug is expanding your waist line:

What kind of drugs cause weight gain?

For weight gain to be listed as a side effect, 5 percent of the patients in a test group taking the medication have to experience it.  Many categories of drugs have well-defined weight-gain profiles, but others, such as certain antidepressants, have mixed results. For instance, selective serotonin reuptake inhibitors (SSRIs), which are prescribed to treat anxiety and depression, originally were thought not to cause weight gain. However, later on, it was found that Paxil and Zoloft do cause weight gain, but Prozac doesn’t.

Why do some drugs cause weight gain?

Drugs that cause weight gain either increase your appetite, causing you to eat more, or slow down your metabolism. The good news is that if you gain weight from these drugs, it is not harder to lose it. So this weight isn’t different than any other weight.



During July, Madelyn Fernstrom, a “Today” contributor and nutritionist, shares tips on how you can watch your weight and still enjoy food.

For more on health, dieting, nutrition, and medical news, check out Today’s health section.


What can be done if the drug is causing weight gain?

Before you start a new medicine, ask your doctor if other patients who have been prescribed the drug have reported weight gain. Even if weight gain is not a formal side effect included on the medication’s packaging, your doctor may know of patients who have experienced weight gain. Make sure you ask. And find out if your doctor is open to prescribing other medication should you happen to gain weight.

What should I do if I gain weight?

If you suspect that you’re adding extra pounds, don’t stop taking your medication. Call your doctor, and ask her if there is another drug you could take instead. Unfortunately, one of the major reasons patients stop taking their medication is because they’ve gained weight — whether or not the drug is responsible. So remember, if you’re taking a drug for a medical condition, don’t stop taking your medication. Talk to your doctor to determine if the drug is causing your weight gain. And if it is, ask your doctor to prescribe a different drug.

What can I do if my medication stimulates my appetite?

  • Be a thoughtful eater. In other words, think before you eat. Before you put a morsel in your mouth, stop and think if you are really hungry.
  • Focus on eating filling, low-calorie foods that will make you feel satisfied, but won’t make you fat. Eat vegetables and fruits, instead of candy, sweets or snack foods.
  • Chew a stick of sugarless gum if you feel a hunger pang.
  • Drink low-calories beverages.
  • Increase your daily physical activity. Take the stairs instead of the elevator. Walk to the corner store instead of driving there. This will offset the extra calories you may consume.
  • Exercise regularly. Three or four times a week, do some aerobic activity: run on a treadmill, go to an exercise class or do yoga.
  • While there is nothing you can do to alter the effect some drugs have on your resting metabolic rate, exercise will burn extra calories and give your metabolism a temporary boost.

What drugs are known to cause weight gain?

If you’re not eating more or exercising less but you’re still gaining weight, your medication may be responsible. Here are some drugs and drug classes that are known to have weight gain as a side effect.

  • Antidepressants
  • Antipsychotics
  • Anti-seizure drugs
  • Anti-migraine
  • Diabetes drugs
  • Blood pressure agents
  • Anti-inflammatory (steroids)
  • Hormone therapy (like tamoxifen)
  • Antihistamine


Some years ago, I did some studies that showed that tricyclic antidepressants (like Elavil and Tofranil) caused a drop in metabolic rate of up to 10 percent. Translated into calories, this is a pound every seven to 10 days, if you don’t change your diet. These older types of antidepressants affect neurotransmitters, causing a broad range of side effects including significant weight gain. Newer antidepressants don’t have the same side effect. While Paxil and Zoloft do cause some weight gain, other SSRIs, like Prozac, Celexa and Lexapro, don’t. For Paxil and Zoloft, the weight gain can add up to five to 40 pounds a year. Some people do experience weight gain with Lexapro or Celexa, but most don’t. In this case, it is not a surprise to have idiosyncratic responses, since the chemical structure of all the SSRIs is so similar.

Newer drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs), don’t appear to have weight gain as a side effect. In fact, Meridia, a weight-loss drug, is an SNRI. Another SNRI, Effexor, has no weight-loss properties, but it is an antidepressant. This shows that tiny changes in chemical structure can have big effects on the brain.

Antipsychotic drugs and other mood stabilizers

Patients who have bipolar disorder, schizophrenia or other psychotic disorders may be prescribed Zyprexa (olanzapine) or Risperdal. Both drugs are associated with weight gain, but they are better than older ones, such as Haldol. While they all cause some weight gain, the new ones are not as sedative. These drugs stimulate appetite and may slow down the patient’s metabolic rate.

Lithium is well known for causing weight gain: One-third to two-thirds of patients who take this drug experience weight gain. It increases appetite, slows metabolism, and increases fluid retention. (While water weight isn’t true weight gain, it makes the patient feel bloated and fatter.) Patients on lithium can gain 20 to 30 pounds — or even more — in a year.

Anti-seizure drugs

A common anti-seize medication, Depakote (valproate) can cause a patient to gain up to 60 pounds in a year. A newer drug, Topamax (topirimate), has a different side effect — weight loss. This can be a problem for patients who need to maintain their weight, or even gain a few pounds to stay healthy.

Anti-migraine medication

Weight gain can be a side effect in the beginning.


Weight gain can occur some times.

Beta blockers

Drugs to control blood pressure, such as Atenolol, can sometimes cause weight gain.


Steroids include such drugs as glucocorticoids and cortisone. For patients who need to take these drugs for the long-term treatment of rheumatoid arthritis or chronic inflammation, they can gain as much as 100 pounds in a year. Patients report that they have increased hunger on steroids. While it is likely that these drugs also affect metabolism, it is not known exactly how. Even transplant patients taking anti-rejection drugs (anti-inflammatory drugs) seem to experience some weight gain.  

Insulin and other diabetic drugs

Insulin is a “fat sparing” hormone, so the body tends to gain weight with insulin or insulin promoters (like Actos). In contrast, for those with early type 2 diabetes, or metabolic syndrome, Glucophage (metformin) seems to help with weight loss. Many diabetics try to lose weight, so they won’t have to take either Actos or insulin. Patients who do take these drugs can gain 40 pounds in a year.

Remember, if you suspect that you’re adding extra pounds, don’t stop taking your medication. Call your doctor, and ask her if there is another drug you could take instead.

Do antidepressants cause weight gain?

Sally AnscombeGetty Images

Weight gain is a possible side effect of nearly all antidepressant drugs. However, it is important to understand that everyone responds to antidepressants differently, meaning some people will gain weight while taking certain antidepressants, while others don’t.

The first thing to realise is that the relationship between antidepressants and weight gain is actually reliant on several factors.

If you are taking antidepressants and are concerned about weight gain, it is important that you do not stop taking the medication. Speak to you doctor and they can then help switch you to an alternative that is less likely to cause weight gain.

Why do antidepressants make you gain weight?

Depression and appetite

Depression can have a big influence on a person’s appetite. In fact, appetite is one of the key areas that doctors ask about when they are making a diagnosis of depression. Some people might eat more, meaning that they put on weight when they are depressed. They also might be more inactive due to their depression, leading to weight gain. More commonly though appetite is reduced, so people will often lose weight.

In these patients when they are started on an antidepressant, their mood improves over the weeks and months of taking the medication and so the poor appetite also improves and as a result their weight increases.

It’s not the antidepressant that is causing the weight gain directly.

It’s not the antidepressant that is causing the weight gain directly – it’s the fact that it’s treating someone’s low mood, which was causing loss of appetite. In this way, you could argue that the antidepressant isn’t strictly responsible for weight gain – it’s just treating the underlying cause of weight loss. So, people tend to return to their usual eating patterns and therefore their usual weight – they don’t put on excessive weight and don’t become obese, but still, a weight gain has been noticed and so this contributes to the idea that antidepressants are causing weight gain.

Passage of time

There is also the fact that people are sometimes on antidepressants for several years and we know that as people age, they tend to put on weight. So, in some people the weight gain noticed will be done to a natural increase in weight that would have happened anyway, but because they are on the antidepressant, they wrongly assume that this is the cause.

Antidepressants and weight gain

A 2018 study found that people taking antidepressants were 21% more likely to put on weight than those who weren’t prescribed antidepressants. An antidepressant called mirtazapine was associated with the most weight gain. However, the study did not prove that antidepressants caused the weight gain directly, as it may have been influenced by other factors such as lifestyle or habits. The study used data from GP prescriptions, so there was no way of knowing whether those people had taken their prescription medicines or not.

People taking antidepressants were 21% more likely to put on weight.

However, we do know that some antidepressants can have a direct impact on weight. The exact mechanism by which they do this isn’t well understood. One possible explanation is that antidepressants interfere with the neurotransmitter serotonin, which is also involved in controlling and regulating hunger. Everyone is different though. Research has shown that only a minority of people put on weight while on antidepressants and so it is by no means inevitable.

Which antidepressants cause the most weight gain?

It’s true that some psychiatric medications that are prescribed do have a big impact on people’s weight. Antipsychotics, for example, which are used to treat psychotic illnesses such as schizophrenia, bipolar or psychotic depression, very commonly make people gain weight. People often get confused and lump all psychiatric medication together and so this too has helped perpetuate this idea that antidepressants will cause increased weight.

Not all antidepressants are equal and studies have shown that some are more likely to result in weight gain than others. There are different classes of antidepressants, and within each class, there are different types:

• Tricyclic antidepressants are an older class and are less commonly prescribed now due to their side effects. Of this class though, amitriptyline, imipramine and doxepin are more likely to cause weight gain.

• Of the monomaimine oxidase inhibitors (MAOIs) – an older class of medication that, again, is less commonly prescribed and tends to be used only when other types haven’t worked, phenelzine is more likely to cause weight gain.

• Of the selective serotonin reuptake inhibitors (SSIRs), the most commonly prescribed class of all the antidepressants, only paroxetine has been shown to increase weight. The internet is full of rumours about other SSRIs causing weight gain, but there’s not enough evidence to support that this is the case.

    There are some other, antidepressants that don’t fit neatly into any of these other categories) and one of them, mirtazapine, has been shown to consistently cause weight gain. This should therefore be discussed before it is prescribed.

    Weight gain is not always a bad thing. In patients who are very underweight, such as older patients who maybe haven’t been eating for a while, this side effect can be very helpful as it increases their appetite and so they become fitter and stronger. For this reason, doctors will often use mirtazapine in people who are underweight and have low mood and need to increase their weight. The one time this isn’t helpful is in anorexia where it would be incredibly distressing for the patient to suddenly put on weight like this, so for this reason it’s rarely used in eating disorders.

    The takeaway

    If weight gain is a concern, then it’s important to mention this to your doctor when they are deciding what medication to prescribe as this will help inform their decision and they can steer away from medications such as mirtazapine that are more likely to cause this.

    Finally, it’s important to remember that the weight gain is as a result of increased appetite and calorie intake and possible reduction in activity. This means that by monitoring closely what someone is eating, ensuring they are not eating too much and that they are exercising, even patients who have found they have been susceptible to weight gain can get on top of it.

    Last medically reviewed: 08-06-2020

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    90,000 Is there a relationship between sertraline and weight gain?

    Sertraline is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of common mental illnesses such as depression, obsessive-compulsive disorder, premenstrual dysphoric disorder, and panic attacks. It works by blocking the reuptake of serotonin in the brain, leading to loss of symptoms of depression. There is a link between sertraline and weight gain, and weight changes have been reported as one of the side effects of the drug.The link between sertraline and weight gain is a major concern for patients taking this drug.

    SSRIs were originally prescribed to aid weight loss in obese people. Studies have shown that long-term use of SSRIs can promote weight gain, causing symptoms similar to hypoglycemia, including hunger, dizziness, and headaches. The exact mechanism is not known, but SSRIs are generally thought to increase the patient’s cravings for carbohydrates and decrease the body’s insulin sensitivity, causing weight gain. Insulin resistance causes weight gain around the midsection and decreases the body’s metabolism. The guidelines distributed with sertraline recommend that patients discuss all side effects, including weight gain, with their doctors if the side effects do not diminish over time.

    Sertraline is usually initially prescribed at a dose of 50 mg once a day. This dose can be increased by 50 milligrams every week until reaching a maximum of 200 milligrams per day. The association between sertraline and weight gain increases with increasing dosage.

    Weight gain is generally considered a serious side effect of sertraline. Studies have shown that the average weight gain is 15-20 pounds (6.8-9.1 kg) in patients taking sertraline. Weight gain can cause poor self-esteem, health problems, and depression, which is counterproductive when taking an antidepressant. The purpose of an antidepressant is to reduce the patient’s depressed mood. The link between sertraline and weight gain can derail these efforts.

    There are several ways you can limit the weight gained while taking sertraline.Sertraline increases the patient’s need for carbohydrates, so he or she should limit the intake of high-calorie foods and sweets. A diet and exercise regimen that minimizes calorie intake and helps burn calories can help neutralize any weight gained while taking sertraline. Exercise also improves a person’s depressive tendencies, making them feel better and healthier.

    The association between sertraline and weight gain is not the only side effect for this medication.Sertraline, prescribed for mood disorders, includes other side effects such as drowsiness, dizziness, trouble sleeping, and decreased sex drive. These side effects diminish over time. Any patient who experiences stiff muscles, nausea, headache, trouble concentrating, or hallucinations while taking sertraline should see a doctor immediately.


    90,000 Research: Taking Antidepressants Leads to Weight Gain – Social Responsibility

    Widespread use of antidepressants may contribute to an increase in obesity in developed countries. Those who take long-term depression medications are 21% more likely to be overweight. This is the conclusion made by the doctors of King’s College London. The work was published in the pages of the medical journal The BMJ. This is reported by The Independent.

    “The widespread use of antidepressants may be one of the reasons for the long-term increase in the weight of the world’s population,” – said one of the co-authors of the work, Martin Gulliford.

    A study found that the risk of weight gain increased after 2–3 years of antidepressant medication.The risk of developing obesity and the appearance of extra pounds in such patients was 29% higher.

    As noted by the authors of the work, the findings suggest that antidepressants should be used less frequently in the treatment of mild forms of depression. Cognitive behavioral therapy and exercise should be a priority in such cases.

    In the study, doctors relied on data on the health status of 300 thousand British patients from 2004 to 2014. The information included data on antidepressant drug intake by patients and their body mass indices (BMI).The researchers adjusted for other factors that can affect weight – age, chronic illness, smoking and other medications.

    Weight gain of 5% of body weight or more during the year was 8.1% among patients not taking antidepressants. Among those who took medication to combat depression, the figure was 11.2%. After 3 years of taking antidepressants, the risk of gaining 5% of body weight per year increased to 46%. Research has shown that the risk of being overweight is greatest in the second and third year of antidepressant use.The risk also remains elevated over the next 6 years.

    Scientists analyzed the effect on body weight of taking 12 common types of antidepressants. So, the drug mirtazapine (another name is remeron) in half of the cases led to an increase in the weight of patients by at least 5% of the body weight before taking the drugs. The drug citalopram increased the risk of weight gain by 26%.

    According to the Organization for Economic Co-operation and Development (OECD), most of the antidepressants are consumed by the inhabitants of Iceland.For every 1,000 Icelanders, there are 118 people taking anti-depression drugs. The top five also includes Australia, Portugal, Canada and Sweden. In the sample of the OECD study, 35 member states of the organization are marked.

    Meanwhile, in the ranking of countries according to the level of happiness of the World Happiness Report, the states of Northern Europe, Australia and Canada have also taken leading positions for several years. For example, Iceland is the leader in the consumption of antidepressants in the ranking of countries in terms of happiness in 2018.took 4th place. In 2017 and 2016, Icelanders were on the 3rd line of the happiest countries in the world.

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    90,000 Weight gain and medication

    Increase in body weight caused by taking medication.

    A number of medications can cause weight gain, especially psychotropic, antiepileptic, hypoglycemic and hormonal drugs.

    Psychotropic drugs. Psychotropic drugs have different effects on body weight, which was confirmed in a meta-analysis of 81 studies using antipsychotics. Among the classic psychotropic drugs (first generation), it was found that the leader in weight gain after 10 weeks of therapy was the drug thioridazine (weight gain 3.2 kg). But the medication molindone did not cause weight gain.

    Of the nonclassical (second generation) antipsychotics, drugs such as clozapine and olanzapine had the greatest effect on weight gain (weight gain 4.4 and 4.2 kg, respectively), followed by risperidone (2.10 kg gain). No weight gain was observed with ziprasidone. Lithium (a psychomimetic), a mood regulator used in the treatment of bipolar disorders, has been associated with weight gain.

    Antidepressants. Tricyclic antidepressants such as amitriptyline, chlomipramine, doxepin, and imipramine have been shown to significantly increase weight.

    Reception of selective serotonin uptake inhibitors (SSRIs), insignificantly affects the change in body weight.Taking fluoxetine and sertraline for a short period of time resulted in weight loss. Conversely, long-term use of some selective serotonin reuptake inhibitors (SSRIs), but not all, may contribute to weight gain, as was confirmed in a sample study of 284 depressed patients treated with fluoxetine, sertraline, or paroxetine for 26-32 weeks. A significant increase in body weight was observed in the group of patients taking paroxetine, while a slight increase and decrease in weight was observed among patients taking sertraline and fluoxetine, respectively.

    Antiepileptic drugs . The antiepileptic drugs valproate (valproate acid) and carbamazepine, which are commonly used in the corrective treatment of bipolar disorders, contribute to weight gain. Gabapentin can also cause weight gain. Topiramate and zonisamide do not have this effect.

    Diabetic drugs. Insulin stimulates weight gain, possibly by lowering blood glucose (hypoglycemia) and by sulfonylurease, which increases insulin release, which also contributes to weight gain.Thiazolidinediones such as pioglitazone and rosylitazone also contribute to weight gain. Metformin, on the other hand, causes small but significant weight loss in patients with impaired glucose tolerance during prophylactic diabetes regimens.

    The effect of insulin is dose-dependent, which has been confirmed in diabetes control and treatment studies, where there was an increase in weight of 5.1 kg in patients in the intensive care group and 2.4 kg in patients with the usual course of treatment.

    Other medicines. Other drugs that promote weight gain include the following drugs: cyproheptadine (an antihistamine), beta blockers (heart drugs), and glucocorticoids (hormonal drugs).

    The side effect of medications causing weight gain is not due to the caloric content of the pills, but due to changes in the rate of metabolic processes in the body and appetite.

    Sertraline and Weight Gain: What You Need to Know

    Sertraline Weight Gain

    Medical Examination: Christine Hall, FNP

    Written by our Editorial Team

    Last Updated 25.05.2021

    Sertraline, marketed under the brand name Zoloft®, is a widely used antidepressant that belongs to a class of drugs called selective serotonin reuptake inhibitors, or SSRIs.

    Like other antidepressants, sertraline can cause certain side effects. One of the potential side effects of sertraline that you may be aware of is weight gain.

    Below we have discussed the relationship between sertraline and weight gain and what you can expect if you are prescribed this medication.

    We also explained what you can do to reduce your risk of gaining weight after you start taking sertraline or other drugs. antidepressants.

    Sertraline and Weight Gain: The Basics

    SSRIs and other antidepressants have long been associated with changes in body composition and weight gain.

    Although newer antidepressants such as sertraline are not as closely associated with weight gain as older drugs, research does show that there is a link between sertraline use and weight gain.

    In a 2016 study published in the Journal of Clinical Medicine, researchers compared different antidepressants to assess their effect on body weight.

    Sertraline was one of several drugs associated with weight gain, with users of this drug experiencing moderate weight gain over two years compared with controls. Fluoxetine, first generation SSRI.

    While this study is not flawless (only a small number of people completed all two years of treatment), it does show that sertraline can and often does contribute to weight gain.

    Why does sertraline cause weight gain?

    Although scientists and healthcare professionals have long known that antidepressants can cause weight gain, there is little evidence to show why this happens.

    Weight gain occurs when people consume more calories from food and beverages than they can burn through physical activity.

    Calorie intake and activity level can be influenced by various environmental factors, including access to certain types of food, large average portions, and lack of exercise.

    Diseases such as hypothyroidism, Cushing’s syndrome, and polycystic ovary syndrome (PCOS) can also contribute to weight gain under certain circumstances.

    There is currently no evidence that sertraline adversely affects your metabolism.

    In one 2009 study, researchers found that sertraline did not significantly affect thyroid function, limiting any potential metabolic effects.

    One theory is that antidepressants like sertraline can stimulate your appetite and make you feel more hungry than usual by affecting your ability to suppress the urge to eat.

    This means that if you are taking sertraline or another antidepressant, you may feel less satisfaction after eating, which will result in you eating larger meals and taking fewer steps to control your total calorie intake.

    Over time, this increase in calorie intake can lead to weight gain if you also do not increase your activity level.

    Because medications such as sertraline are often prescribed long-term, even a small increase in appetite can ultimately significantly affect your weight.

    Another theory is that sertraline and other antidepressants can cause weight gain by reversing the weight loss that some people experience when depressed.

    Emotions such as depression can often lead to loss of appetite. If you have lost weight due to decreased appetite due to depression, you may gain weight as your appetite regains after starting treatment with sertraline or another antidepressant.

    It is also possible that sertraline and other SSRIs can block the action of hormones that control sodium and fluid in the body, resulting in fluid retention.

    In short, while weight gain is a known side effect of sertraline and several other antidepressants, experts are not yet fully understood why.

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    Other SSRIs and Weight Gain

    Sertraline is not the only antidepressant that can cause weight gain. Many other antidepressants, including other SSRIs, are associated with some degree of weight gain.

    In a review published in the journal Translational Psychiatry, the researchers noted that SSRI users gained an average of 4.6% of their body weight over four years of treatment.

    Another study found that certain antidepressants, such as citalopram, often cause carbohydrate cravings and significant weight gain during treatment.

    As for specific SSRIs, the data vary. Can escitalopram (marketed as Lexapro®) cause weight gain? Relatively little, according to one study, which found that people with depression who received escitalopram gained an average of just 0.34 kg (0.75 lb) in six months.

    Similarly, SNRI antidepressants such as duloxetine (marketed as Cymbalta®) can also cause weight gain. In one review, researchers noted that duloxetine resulted in slight weight gain with long-term treatment for depression.

    Simply put, weight gain is a fairly common side effect of both SSRIs and other antidepressants, rather than an isolated side effect that occurs only with sertraline.

    Antidepressants Causing Weight Loss

    Although most antidepressants are associated with weight gain, some drugs used to treat depression appear to promote weight loss.

    In particular, the drug bupropion (commonly marketed as Wellbutrin®) has been linked to weight loss in several studies.

    In a study published in the journal Obesity Research in 2001, researchers compared bupropion with a non-therapeutic placebo to evaluate its effectiveness in treating obesity.

    They found that study participants who used bupropion achieved greater average weight loss than those who took placebo.

    After eight weeks of treatment, women taking bupropion lost an average of 6. 2 percent of their initial body weight compared to an average weight loss of 1.6 percent for women in the placebo group.

    A review published in the journal Pharmacological Research notes that bupropion may affect areas of the brain responsible for controlling food cravings and other aspects of eating behavior that affect body weight.

    If you are prescribed an antidepressant and notice that you are starting to gain weight, you may want to talk to your healthcare provider about switching to another medication with a lower risk of weight gain.

    Avoiding weight gain from sertraline

    While some weight gain from sertraline may be unavoidable, there are a few steps you can take to minimize the weight gain from your medication:

    • Weigh yourself before how to start .Make sure you know how much you weigh before you start taking sertraline. This will make it easier to keep track of any changes in your weight that occur while you are taking this medication. Try weighing yourself in the morning – ideally after going to the bathroom and before eating – for the most accurate measurement.

    • Maintain your normal eating habits . Sertraline can affect your appetite, making you feel less satisfied with your food than usual.To minimize weight gain, try to maintain your previous eating habits such as food choices, serving sizes, and meal times.

    • Stay active . If you are currently exercising, it is best to continue exercising as usual after starting treatment with sertraline, unless your doctor advises you not to do so. In addition to weight management, exercise can help relieve some of the symptoms of depression and anxiety.

    • Weigh yourself weekly, not daily . Your weight fluctuates significantly during the day, which means that you can be several pounds heavier in the evening than in the morning.

      For this reason, it is better to track any changes in your weight over time rather than daily. Try to track your weight loss every week or month to see if there is a noticeable upward or downward trend.

    • If you gain weight, tell your doctor. . If you notice significant weight gain after starting sertraline, it is important to talk to your healthcare provider. To control their weight, they may recommend adjusting your diet, changing your activity level, or making changes in the way you use bupropion. In some cases, your healthcare provider may recommend using a different type of antidepressant.

    • If you are losing weight, tell your doctor.. Likewise, if you notice significant weight loss after starting sertraline, it is also important to talk to your doctor.

    Although SSRIs such as sertraline have a reputation for causing weight gain, the right combination of habits and careful observation can help you maintain your weight on antidepressants.

    Using the tactics described above, you can prevent or minimize any changes in your weight after you start taking sertraline.

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    Learn more about Sertraline

    Sertraline is one of the most common medications for depression. It is used by millions of people in the United States and around the world and has a good record of safety and efficacy.

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    Although some people gain mild weight when using sertraline, following a healthy diet and lifestyle while using this medication can help you stay fit and maintain your current body composition.

    If you notice any change in weight while taking sertraline, it is important to see your doctor.

    You can learn more about how sertraline works, its effects, side effects and more in our detailed Sertraline 101 guide.

    If you are feeling depressed, anxious, or distracted and want to speak with a specialist, you can contact a licensed online mental health provider through our online mental health service.

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    This article is for informational purposes only and does not constitute medical advice.The information contained in this document is not intended to substitute for, and should in no way be relied on, professional medical advice. Always talk with your doctor about the risks and benefits of any treatment.

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    90,000 More on the side effects of antidepressants: dpmmax – LiveJournal

    Yesterday I began to tell you exactly how the use of antidepressants is fraught with sideways.Yes, this is another reason why the search for the perfect drug in this class continues. Along with the main one: to fight depression reliably and for a long time. And that is not always the case. So let’s continue.

    8. Suicide. Actually, a rather controversial effect, although since 2004 antidepressant manufacturers have been obliged to indicate its risk as a possible side effect, and write directly on the packaging a warning about the increased risk of suicide in children and adolescents. The trick is that depression itself carries the potential for suicide, and it’s not about the antidepressant. There are at least two potentially possible and potentially dangerous moments during the course of the illness while taking these drugs. The first is when, despite taking pills, the depth of depression increases so much that a person begins to think about suicide, and then commits it. The second is the opposite of the mirror. Let’s say there was a person in the deepest depression. So deep that I lay quietly in a depressive stupor, I already refused to eat or drink.And then the treatment began, the antidepressant worked, the depth of depression decreased, the person had the opportunity to get out of bed and at least do something. The only trouble is that the opportunity to move has appeared, but the ability to think constructively and assess your prospects soberly is not yet there. And the soul really hurts, and this pain, believe me, is not weaker than the physical one. So such a person makes a suicidal attempt, taking advantage of the fact that the strength has appeared to do this.

    9. Overdose toxicity. If you remember, in the literature of the beginning of the last century, especially detective literature, it was fashionable to poison book heroes with morphine or barbiturates. Both, by the way, were still quite widely used in medicine at that time, which means they were in pharmacies. This means that both well-wishers have complete freedom of action, and those who have decided to die themselves – quietly and in a dream. Why, in fact, they once found a replacement for barbiturates by discovering tranquilizers: the range of doses for barbiturates from therapeutic to lethal is very narrow. Antidepressants, I must say, in this regard are safer than barbiturates and tranquilizers.But you shouldn’t expect anything good from their overdose either. The mood will not jump up sharply, and suicide with a smile on the lips will not work. Although the suicide itself, if you try, can happen. In this regard, amoxapine, maprotiline, and desipramine have the highest hazard index (the number of deaths per thousand poisonings with antidepressants). Antidepressants about three rings are more toxic than those with a small and large biochemical bend. But it’s better not to joke with those either.

    10. Influence on the sexual sphere. Here I must say that depression in itself somehow does not contribute to normal potency and strong libido – not up to that, everything is bad by default. And if the patient begins to complain that the antidepressant prevents him from being normally interested and interacting with a partner, then everything is not so bad anymore. But in general, there is such a problem. Reduces most antidepressants and libido and potency. As a rule, only for the duration of their intake (perhaps, with the exception of trazodone, which is even used to treat problems with potency in men), but in rare cases, the effects can last longer.What can you do: All antidepressants that interfere with the seizure of serotonin or norepinephrine cause sexual dysfunction. The most common causes of this problem are citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine. Imipramine is the same, but weaker than the five named antidepressants. Bupropion has the lowest sexual side effects of any modern antidepressant.

    11. Weight gain. Unfortunately, there is such a side effect, although not everyone knows about it.Among those with a small bend, the most risky in this regard is paroxetine, among tricyclic ones – amitriptyline. However, on average, weight gain with amitriptyline, sertraline and fluoxetine is similar. By the way, at first, especially when taking the same fluoxetine and paroxetine, exactly the opposite happens: the appetite becomes less, the weight decreases, and so on for 4 months. But then this effect goes away, and the weight begins to grow. Amitriptyline and mirtazapine contribute to weight gain regardless of the duration of use – in both short-term and long-term treatment.Imipramine and bupropion, on the other hand, promote weight loss or relatively slow weight gain with short- and long-term treatment.

    12. Sweating. Not fatal, but, you must admit, it is unpleasant, especially when the crisis is over, and we are improving the quality of life. Sweating occurs in 10% of patients taking low-bend antidepressants (SSRIs), venlafaxine, and tricyclics.

    13. Sleep disturbance. Here the action is very heterogeneous, multidirectional, depending on what kind of antidepressant it is.Sometimes its effect on sleep is used specifically – for example, as the sedative effect of tricyclic antidepressants, the hypnotic effect of agomelatine and mirtazapine. Or, as with the treatment of narcolepsy, venlafaxine’s ability to reduce REM sleep is exploited. But bupropion, due to its activating effect, is quite capable of causing insomnia.

    14. Retention of urination. An unpleasant moment, especially if you already have urological problems. And a number of antidepressants, especially the old ones, like amitriptyline and imipramine, are sinful for this.

    There is one more side effect, but I will write about it separately – it requires more detailed explanation. If interested, of course.


    Of all psychiatric disorders, depression is considered the most underestimated. 10–20% of all people experience this disease at least once in their life. Among the elderly, the prevalence of depression is increasing and reaches 15–25%. The main problem of depression is the underdevelopment of its diagnosis and the lack of psychiatrists.Therefore, at first, we considered it unnecessary to immediately load you with the classification of antidepressants, but pay attention to the pathogenesis of this disease. It is the knowledge of the theory that helps to understand why such groups of pharmaceuticals as sedatives and anxiolytics are not effective enough in monotherapy.

    For a long time, electroshock therapy was actively used in the treatment of depression, the purpose of which was to increase the metabolism of neurotransmitters in the brain. Surprisingly, 75% of patients did experience symptom improvement.For example, the famous pianist Vladimir Horowitz suffered from depression for years, and it was electroshock therapy that helped him return to the stage.

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    From 15 to 30% of all depressive disorders tend to be chronic and recurrent. That is why most of the therapy regimens are designed for a long period of time. Since some of the depressive disorders are associated with other diseases, it is necessary to pay special attention to the possibility of combining different groups of pharmaceuticals.

    There can be several reasons for depression. This condition is characterized by a number of physiological changes: the concentration of norepinephrine decreases in the tissues of the body , the number of serotonin receptors decreases and their affinity for ligands decreases (5-HT 2A, 1B, 1A in the cerebral cortex – if you are not sure you can it is easy to say which receptor is responsible for what, we recommend re-reading our article about serotonin – https://goo. gl/iiUYKk), the activity of corticotropin and glucocorticoids increases, atrophy of the frontal and prefrontal cortex of the hippocampus is observed, there is also a decrease in the number of connections between neurons, in the frontal cortex, the number of blood vessels decreases, the concentration of melatonin decreases, which leads to sleep disorders .It is worth noting that depressive disorders are often inherited (40–50% of unipolar and 60–70% of bipolar disorders). However, genetic penetrance, as in the case of other mental illnesses, is reduced. Therefore, 90% of patients do not have similar cases of the disease in the family circle. The disorder increases with the duration of the illness.

    In 1965, the American physician Shildkraut suggested that depression may be based on processes leading to a decrease in the concentration of serotonin and norepinephrine in the synaptic cleft.In humans, in the posterior nucleus of the suture and in the locus coeruleus of each hemisphere of the brain, there are up to 165,000 noradrenergic and 55,000 serotonergic neurons. That is why even a small decrease in the number of these neurons is already capable of causing characteristic symptoms. Also, with depression, the production of presynaptically located alpha-2-adrenergic receptors increases. When norepinephrine acts on autoreceptors and serotonin on heteroreceptors (neurotransmitters are released from the same neuron), the whole process slows down according to the principle of negative feedback, which only increases the lack of these neurotransmitters in the synaptic cleft.Lack of adrenaline, in turn, leads to apathy and a feeling of fatigue.

    Serotonin is credited with participating in the formation of contacts between neurons. Many indicators associated with serotonin metabolism, such as, for example, a decrease in the concentration of serotonin and its receptors, mutations in genes encoding serotonin transport systems, and decreased production of serotonin-binding proteins, such as p11, correlate with the severity of depressive disorder. It is believed that a decrease in dopamine concentration also affects the development of depression, but is not its root cause.

    Depressive disorders are also characterized by a decrease in neurogenesis , mainly due to stress-induced hypercortisolism and impaired function of the brain derived neurotrophic factor (BDNF). As a result of experiments, it was proved that an increase in the synthesis of BDNF helped to overcome the symptoms of depression caused by a deficiency of this factor. Scientists were able to prove that the transcriptional repressor GATA1 is able to reduce the number of synapses in the prefrontal cortex of animals and thus provoke the development of depressive symptoms in them.As we already wrote in our infographic (https://goo.gl/611CMc), the development of this disease is affected by disruption of the hypothalamic-pituitary axis , as well as an increase in neuronal cholinergic transmission. Many pharmacological drugs, in turn, are capable of causing depressive disorders (glucocorticoids, very high or low concentrations of gestagens, antipsychotics, anticonvulsants, as well as antihypertensive drugs, fluoroquinolones and interferons). Refusal from opioids and benzodiazepines after long-term use also causes characteristic symptoms.

    Having examined these mechanisms, we can finally move on to the main point and answer the question – what properties should the drugs of this group possess?

    All antidepressants, except for lithium and agomelatine, lead to an increase in the concentration of norepinephrine and / or serotonin in the synaptic cleft. This can be done in several ways: by blocking the transport systems that carry these neurotransmitters back to the neuron, by decreasing the activity of alpha-2-adrenergic receptors (as mentioned above), by decreasing the activity of the enzyme responsible for the breakdown of serotonin and norepinephrine (MAO A, MAO A / B ), as well as affect the 5-HT 2C serotonin receptor.

    Norepinephrine enters the presynaptic terminal via a special highly selective NET transporter and partially through microglial cells using less selective transport systems. A small amount of norepinephrine is able to diffuse into the intercellular space, and from there directly into the blood. With depression, the concentration of norepinephrine decreases. Antidepressant drugs are able to displace norepinephrine from the connection with the receptor, which increases its concentration in the synaptic cleft and increases its interaction with receptors.On the part of the adrenergic system, a number of changes are also observed during antidepressant therapy: the production of postsyntaptic alpha-1 and beta receptors increases and the number of presynaptic alpha-2 receptors decreases. However, these changes are not typical for therapy with all types of antidepressants.

    Serotonin is released back into neurons via the SERT protein, which, as you might guess, can also be blocked to increase the amount of serotonin in the synaptic cleft.The effect of antidepressants on this system is not the same, since all receptors are very different in their structure and location. However, we can say that under the action of antidepressants, the production of postsynaptic 5-HT2A receptors in general decreases, which correlates with the anxiolytic effect of these drugs, the production of presynaptic 5-HT1A receptors decreases (they have an inhibitory potential according to the principle of negative feedback), and 5-HT2C is blocked. receptors, which leads to the effect of anxiolysis and increased release of norepinephrine and dopamine in the prefrotal cortex.

    Direct antagonists of presynaptic alpha-2-adrenergic receptors mianserin and mirtazapine block the processes of self-inhibition of norepinephrine release, which also leads to an increase in norepinephrine in the synaptic cleft. The number of presynaptic alpha-2 receptors decreases, and postsynaptic alpha-2 receptors begin to bind adrenaline more strongly.

    Antidepressants, except buspirone, do not directly affect dopamine metabolism, therefore they do not have antipsychotic potential (except that trimipramine is able to block the dopamine D2 receptor). But, nevertheless, dopamine transmission increases under the influence of antidepressants. This is due to the fact that the norepinephrine transport protein NET is also capable of binding to dopamine. The D2 receptor agonist pramipexole is approved for use in depressive disorders in the context of Parkinson’s disease.

    It should be noted that many of the mechanisms of action of antidepressants remain unexplored. For example, it is impossible to predict the strength of its action by the chemical structure of an antidepressant.The therapeutic effect of the drug hardly correlates with the strength of the blockade of the serotonin and norepinephrine transporter proteins. Also, it was not possible to note the relationship between the number of monoamine receptors and the severity of the clinical effects of antidepressants.

    Side effects are mainly pronounced in two groups of antidepressants – alpha-2-adrenergic receptor antagonists and tricyclic antidepressants. These two groups of drugs affect not only the receptors that were described in the previous post, but also muscarinic, alpha-1-adrenergic and histamine receptors.It is because of their influence on these systems that many patients refuse to take drugs of these groups, preferring them selective serotonin and / or norepinephrine reuptake inhibitors.

    Tricyclic antidepressants (eg amitriptyline) and alpha-2-adrenergic receptor antagonists have a fairly high affinity for the muscarinic acetylcholine receptors. By blocking them, these substances cause side effects similar to those of atropine: dry mouth (risk of tooth decay when using chewing gum containing sugar), mydriasis and impaired eye accommodation (and, as a result, an increased risk of falls), increased intraocular pressure, constipation , violation of urination, confusion up to anticholinergic delirium with optical hallucinations, tachycardia (enhanced by blockade of alpha-1-adrenergic receptors).In older people, taking drugs that cause xerostomia is especially problematic. They have to constantly drink water, increasingly replacing it with drinks with a high sugar content, which affects the metabolism of carbohydrates, leading to the development of tooth decay and weight gain. Dry mouth is a side effect of more than 500 medicinal substances, among which are mainly anticholinergic (tricyclic antidepressants, antipsychotics, histamine receptor antagonists of the first type), as well as antihypertensive drugs (beta-blockers and calcium channel inhibitors).By observing the rules of oral hygiene and the recommendations of the dentist, you can successfully avoid this side effect. As you might guess, it is better not to combine drugs of these groups with other substances that cause atropine-like effects (antipsychotics, antiparkinsonian drugs, histamine receptor blockers of the first type).

    Blockade of adrenergic alpha-1 receptors by tri- and tetracyclic antidepressants leads to vasodilation, which increases the risk of hypotension.Therefore, these groups of drugs are not recommended to be drunk at night. With heart failure and severe hypertension, orthostatic hypotension caused by antidepressants can be especially acute (in this case, therapy with sympathomimetics ethylephrine and midodrin is recommended). There is also a risk of developing reflex tachycardia and rhythm disturbances, which can increase due to the simultaneous blockade of acetylcholine receptors and the resulting decrease in parasympathetic activity.

    Tricyclic antidepressants and antagonists of adrenergic alpha-2 receptors are capable of blocking type I histamine receptors almost as strongly as selective blockers of this group. This is due to the affinity of the domains binding to these receptors: many substances that are antagonists of the first type of histamine receptors are also antagonists of the muscarinic acetylcholine receptor (this affinity is more pronounced than for the second type of histamine receptor).

    The main consequences of type 1 histamine receptor blockade are sedation and drowsiness. Sedation is sometimes considered not a side effect, but rather desirable, because patients often suffer from anxiety and insomnia, especially at the beginning of therapy. The negative effects, of course, will be impaired concentration and attention, which is very important if the patient needs to drive a vehicle.

    From the media, even the layman knows another side effect of antidepressants – an increase in appetite and a tendency to gain weight.The fact is that the first type of histamine receptors are also found in the hypothalamus and are responsible for appetite. Signals from these receptors control satiety as much as leptin. With their blockade, respectively, this signal weakens, which leads to the fact that the patient is gaining weight. With blockade of 5-HT2A receptors, this effect is especially pronounced. Sometimes patients gain weight from 10 to 20 kilograms, which, of course, affects self-esteem and, thus, the effectiveness of the therapy itself.

    The purpose of taking antidepressants is to increase the effect of norepinephrine, adrenaline and serotonin, which is not without its side effects. Patients are prone to increased sweating, while it increases with the intake of estrogens and the serotonergic opioid tramadol.

    Norepinephrine increases the tone of the sphincter of the bladder, which leads to difficulty urinating. Serotonin causes nausea and diarrhea. Due to the inadequately strong release of antidiuretic hormone when taking some antidepressants, hyponatremia may develop (Parkhon’s syndrome).

    The use of antidepressants (in high concentrations) can lead to an increase in blood pressure. Also, when they are taken, anemia and agranulocytosis may develop. Some drugs, such as venlafaxine and mirtazapine, cause hair loss. There has been a relationship between the use of antidepressants and the development of restless legs syndrome.

    Tri- and tetracyclic antidepressants

    Drugs in this group are non-selective monoamine reuptake inhibitors.This complex name hides the very mechanism of action of these antidepressants.

    This group of antidepressants is the only one that has received its name because of the structure of the molecule. In 1957, the form of the tricyclic antipsychotic agent chlorpromazine was deciphered. This affinity of the structures of antipsychotics such as phenothiazine and thioxanthene explains the affinity of the effects of antidepressants and antipsychotics, such as trimipramine, which also has an antipsychotic effect.

    Recall that drugs of this group inhibit the reuptake of norepinephrine and serotonin by neurons (with the seizure of the former prevailing), inhibit the 5-HT-2A / C-serotonin receptor (anxiolytic effect of clomipramine), and also block the histamine receptor of the first type (sedative effect).In small amounts, they also inhibit the reuptake of dopamine.

    Tricyclic antidepressants have lipophilic properties, which allows them to easily pass through the BBB. In their metabolism, a special role is assigned to the so-called first pass effect, which determines their low bioavailability. TCAs are metabolized in the liver, therefore, in case of overdose, forced diuresis does not work. Under the influence of CYP2D6, tertiary amines (amitriptyline, imipramine) are converted into secondary ones (desipramine, nortriptyline).

    Depending on the type of initial compound, all TCAs are divided into three groups:

    Imipramine type: imipramine and clomipramine.
    Amitriptyline type: amitriptyline, amitriptyline oxide, doxepin, opipramol, trimipramine.
    Desipramine type: desipramine, nortriptyline.

    The TCA effect is not immediately noticeable. In the first week, the sedative component predominates, in the second – the thimeretic, in the third week, their thymoleptic effect is observed.Such inhibition of the effects of TCA action suggests that not all mechanisms of action of these drugs have been studied yet, because the concentration of neurotransmitters in the synaptic cleft increases already on the first day of administration.

    Amitriptyline is used in severe forms of depression. In low dosages (25-50 mg), amitriptyline is also used as a coanalgesic agent for neuropathic pain. Like many other drugs in this group, amitriptyline has a wide range of side effects (see.part 2), which, however, weaken over time. Tricyclic antidepressants also inhibit adrenergic α1-receptors, muscarinic acetylcholine receptors and histamine receptors of the first type. Anticholinergic effects include dry mouth, diuresis disorders, constipation, accommodation disturbances, visual disturbances, increased intraocular pressure, tachycardia and delirium (especially in elderly patients. TCAs are contraindicated in dementia). Development of seizures of central origin is possible.TCAs have a cardiotoxic and negative inotropic effect, which leads to hypotension, an increase in the QRS complex and the development of cardiac arrhythmias. Due to the blockade of adrenergic α1-receptors, the development of orthostatic hypotension is observed. Due to blockade of type 1 histamine receptors, patients experience dizziness, fatigue, weight gain, and appetite gain. That is why taking TCAs is recommended before bedtime. TCAs also provoke the development of Parkhon’s syndrome. Symptoms of a TCA overdose are similar to those in serotonin syndrome: fever, extrasystole, tachycardia, confusion, mydriasis, hallucinations, visual impairment.It is advised to stop this condition with physostigmine, as well as activated charcoal, anticonvulsant drugs, sodium bicarbonate and the infusion of isotonic solutions.

    Nortriptyline is a metabolite of amitriptyline and is more suitable for combination therapy, primarily due to its more weakened anticholinergic action and side effects related to cardiac activity. However, for drugs of the desipramine type, to which nortriptyline belongs, a particularly pronounced thimeretic effect is also characteristic.The drugs of the imipramine type do not differ in this.

    Imipramine is a highly potent inhibitor of the norepinephrine transporter. Due to the fact that it only slightly inhibits type 1 antihistamine receptors, the sedative effect of imipramine is significantly reduced. Its anticholinergic side effects are much less pronounced. Trimipramine also inhibits the D2 receptor and is the only drug in this group with an antipsychotic effect.

    Clomipramine , on the other hand, differs in that it inhibits SERT quite strongly.Associated with this, its anxiolytic action is used in the treatment of obsessive-compulsive disorders.

    Doxepin binds to h2-receptors, inhibiting them, which is used in the therapy of neurodermatitis (off label use), relieving the feeling of itching, and the sedative component helps to fall asleep. The drug is prescribed for alcohol withdrawal symptoms and opioid withdrawal.

    Trimipramine , as noted earlier, is the only one of this group that has an antipsychotic effect, since it is an antagonist of dopamine D2 receptors.

    Opipramol has the structure of a tricyclic antidepressant, but is unable to inhibit either NET or SERT. Its main function is to block the first type of histamine receptors, which causes a strong anxiolytic effect and promotes better sleep without causing addiction like benzodiazepines.

    It should be noted that the blockade of sodium channels (amitriptyline) contributes to the development of cardiac arrhythmias with an increase in the QT interval (but provides an analgesic effect).The blockade of muscarinic acetylcholine receptors is fraught with the development of tachycardia and sympathomimetic effects: increased blood pressure and tremor.

    An increase in the tone of norepinephrine contributes to the development of excited states of the central nervous system up to a convulsive attack. The metabolism of tricyclic antidepressants in the liver leads to an increase in the concentration of liver transaminases in the blood. It is logical to assume that drugs of this group are not prescribed to patients with epilepsy, cardiac arrhythmia in liver diseases, prostatic hyperplasia and glaucoma.

    TCAs are used mainly for endogenous depressions, but at the moment, due to side effects, drugs in this group are rather reserve ones. Abrupt withdrawal of TCAs provokes the development of insomnia and symptoms similar to those of influenza, and there is also a positive correlation between abrupt withdrawal of TCAs with the number of suicides.

    Tetracyclic antidepressants are inhibitors of α2 adrenergic receptors. They are weak inhibitors of NET and SERT, and their ability to block type I histamine receptors causes their sedative effect at the beginning of therapy.Therefore, these drugs have been used for agitated depression. Mianserin and Maprotiline are derivatives of mirtazapine. S – (+) – enantiomers are capable of blocking α2 adrenergic receptors and 5-HT2 receptors. R – (-) – enantiomers also inhibit 5-HT3 receptors. Mirtazapine does not block the uptake of monoamines. Due to its sedative effect in the absence of anticholinergic side effects and only a slight emetic effect, mirtazapine is used in geriatrics mainly as a hypnotic agent that does not affect REM sleep.Mianserin is capable of causing agranulocytosis and aplastic anemias, therefore, when using it, it is recommended to regularly do a blood test. Mirtazapine most often provokes restless legs syndrome and weight gain up to 10 kg in just a few weeks. Like tricyclic antidepressants, tetracyclic antidepressants are contraindicated in epilepsy, renal failure, and glaucoma.

    Selective monoamine uptake inhibitors

    Depending on which neurotransmitter undergoes reuptake, drugs in this group of drugs are divided into several types: SSRIs, SSRIs and SNRIs .

    The side effects of these groups of drugs are significantly less than that of tricyclic antidepressants. Selective uptake inhibitors do not affect the activity of the CVS, and also do not have anticholinergic and pro-convulsive effects. Serotonin syndrome (https://goo.gl/qWHHpM) is a serious side effect. Its symptoms are abdominal pain, fever, tachycardia with increased blood pressure, hyperreflexia, and myoclonus.Death is possible. The cause of the development of serotonin syndrome can be an overdose of drugs that enhance serotonergic effects, in particular the combination of selective serotonin reuptake inhibitors with tramadol, triptans, moclobemide, MAO inhibitors and lithium preparations.


    Venlafaxine and duloxetine block the reuptake of both serotonin and norepinephrine, and both are substrates for CYP2D6.

    Venlafaxine (dosage 75-300 mg per day, half-life – 5 hours, active metabolite – desmethylvenflaxine) is characterized by low bioavailability (less than 20%) when taken orally. At low doses, it is able to inhibit the reuptake of serotonin, at high doses, it is capable of inhibiting norepinephrine, which, however, does not in any way affect its antidepressant potential. Venlafaxine is also able to partially inhibit dopamine reuptake.

    Duloxetine (dosage 30–90 mg per day) blocks the reuptake of both neurotransmitters equally.As you might guess, acting only on the reuptake of neurotransmitters, selective inhibitors of this group do not have atropinergic and sedating effects, in contrast to tricyclic antidepressants. Sometimes patients begin to complain of difficulty urinating, sweating and impaired potency, but this rarely leads to refusals to take medications. These drugs are contraindicated in liver disease, severe hypertension, epilepsy and glaucoma.


    Selective norepinephrine inhibitors (reboxetine, dosage 8-12 mg per day, half-life – 13 hours, active metabolite – desetilreboxetine) increase the concentration of norepinephrine in the synaptic cleft.Because of the many side effects associated with norepinephrine, SNRIs are only used for severe depressive episodes. Reboxetine metabolism occurs with the help of CYP3A4, which limits its use in combination with drugs that affect the work of this cytochrome.


    With a selective blockade of only serotonin reuptake, the antidepressant effect of this group is better expressed.The drugs in this group include citalopram (dosage 10-60 mg per day, half-life – 33 hours, active metabolite – desmethylcitalopram), its more specific to SERT S-enantiomer escitalopram (dosage 5-20 mg per day), sertraline (dosage 50-200 mg per day, half-life 24 hours, active metabolite – desmethylsertraline), paroxetine (dosage 20-60 mg per day, half-life 8-30 hours), fluoxetine (dosage 10-60 mg per day, half-life – 48–96 hours, active metabolite – norfluoxetine) and fluvoxamine (dosage 50–300 mg per day).The latter two drugs are also capable of acting on opioid receptors, providing an analgesic effect. Otherwise, the antidepressant effect of the above drugs is approximately the same. Also, their concentration does not significantly change in renal failure. According to many meta-analyzes, escitalopram and sertraline have the best antidepressant effect, while citalopram has fewer side effects and good efficacy. Escitalopram, depending on the dosage, is able to lengthen the QT interval, which, unfortunately, does not allow the drug to achieve the best effect due to the need to reduce the dosage.Differences in the use of individual representatives of this group are presented in the table attached to the post. Fluoxetine and paroxetine are potent, while citalopram and escitalopram are weak inhibitors of CYP2D6. Blocking this system increases the concentration of tricyclic antidepressants and neuroleptics in the blood, and the effect of tamoxifen (an estrogen antagonist used in the treatment of breast cancer), on the contrary, decreases, since tamoxifen, being a prodrug, is activated in this system in the liver.

    Blocking SERT itself causes a number of side effects, such as, for example, drowsiness and akathisia (internal anxiety due to 5HT2 serotonin receptors), especially at the beginning of therapy. Serotonin is also involved in platelet aggregation. In the platelet membrane, exactly the same serotonin transporter SERT is built as in neurons, therefore, due to a lack of serotonin, its vasoconstrictor effect on 5-HT-2A serotonin receptors decreases.Therefore, the drugs of this group should be used with caution if the patient is sick with chronic inflammatory bowel diseases or is taking salicylic acid preparations (antiplatelet agents) or vitamin K antagonists (indirect anticoagulants). Due to increased stimulation of 5HT-2A serotonin receptors in the posterior field (area postrema) and 5HT-3 receptors in the gastrointestinal tract, these drugs provoke vomiting, which can be stopped by blockers of the 5-HT3 serotonin receptor (ondansetron). It is because of the feeling of nausea that the drugs of this group at the beginning of therapy lead to a decrease in the patient’s weight.Due to the increased secretion of antidiuretic hormone, fluid retention occurs in the body, which leads to a decrease in the concentration of sodium in the blood in the first 4–6 weeks after the start of taking the drugs in 10–20% of patients. Potency disorders are also observed when taking this group of antidepressants.

    Sertraline reversibly reduces sperm quality and causes ejaculation disorders. The reason for this is the indirect antagonism of dopamine receptors, which provokes hyperprolactinemia.

    Dapoxetine is approved for use in premature ejaculation. In this case, the drug was approved due to its side effects. However, in some cases, antidepressants of this group provoke reverse ejaculation (retrograde ejaculation of semen occurs in the proximal direction to the bladder, which can lead to inflammatory processes). Activation of serotonin receptors also affects the dopamine system: patients feel more tired (activation of 5-HT2C receptors reduces the release of dopamine).An excess of serotonin provokes tremors, headaches and osteoporosis, as well as pseudocholinergic dry mouth and especially severe sweating of the scalp. The following fact is interesting: at one time it was observed that an increase in determination and thirst for action with drugs of this group increased the number of suicides. It was assumed that increased readiness for action led to the fact that patients with depression began to make more frequent decisions to commit suicide. But later, one large British study refuted this claim, proving that self-reliance on drugs increases the number of suicides.

    Separately, it is worth noting the drug bupropion (dosage 150-300 mg per day, half-life 20-37 hours, active metabolites – hydroxybuproprion, treohydrobupropion, erythrohydrobupropion), which is mainly an inhibitor of the reuptake of norepinephrine and dopamine, but also affects other transmitter systems.