How does Zoloft affect weight. What are the common side effects of sertraline. Can you manage weight gain while taking antidepressants. Why do SSRIs cause changes in appetite and metabolism.

The Rise of Antidepressant Use in America

The landscape of mental health treatment in the United States has seen a significant shift over the past decade. From 2009 to 2018, the percentage of U.S. adults taking prescription antidepressants rose from 10.6% to 13.8%. This increase reflects a growing awareness and acceptance of mental health issues, as well as improved access to treatment options.

While antidepressants have proven effective in alleviating symptoms of depression and anxiety, they are not without potential side effects. One such side effect that concerns many patients is weight gain, particularly associated with medications like Zoloft (sertraline).

Understanding Zoloft and Its Mechanism of Action

Zoloft, known generically as sertraline hydrochloride, belongs to a class of antidepressants called Selective Serotonin Reuptake Inhibitors (SSRIs). These medications work by increasing the levels of serotonin in the brain, a neurotransmitter crucial for mood regulation, emotional balance, and various cognitive functions.

SSRIs like Zoloft inhibit the reuptake of serotonin, allowing it to remain active in the brain for longer periods. This increased serotonin activity is believed to help alleviate symptoms of depression, anxiety, and other mental health conditions.

Conditions Treated by Zoloft

• Major depressive disorder
• Anxiety disorders
• Panic attacks
• Obsessive-compulsive disorder (OCD)
• Post-traumatic stress disorder (PTSD)
• Social anxiety disorder (social phobia)
• Premenstrual dysphoric disorder (PDD)

Approved by the FDA in 1991, Zoloft is available only by prescription and can be taken orally in pill or concentrated liquid form, typically once daily.

The Link Between Antidepressants and Weight Gain

Weight gain is a common concern for patients taking antidepressants, including Zoloft. While the exact mechanisms are not fully understood, several theories exist to explain this phenomenon:

Serotonin’s Role in Appetite Regulation

Serotonin plays a crucial role in regulating not only mood and anxiety but also appetite. When taking SSRIs, some individuals may experience increased cravings for carbohydrate-rich foods, such as bread, pasta, and desserts. If not balanced with proper diet and exercise, this can lead to weight gain.

Metabolic Changes

Some experts hypothesize that SSRIs may trigger changes in metabolism due to fluctuations in serotonin levels. These metabolic shifts could potentially contribute to weight gain in some individuals.

Improved Appetite with Mood Enhancement

As depression often leads to decreased appetite and weight loss, the alleviation of depressive symptoms may result in a return to normal eating patterns. For some, this could mean an increase in food intake compared to their depressed state.

Is weight gain inevitable with Zoloft use? Not necessarily. The effects of SSRIs on weight can vary significantly between individuals. While some may experience weight gain, others might see no change or even lose weight.

Common Side Effects of Zoloft

While weight gain is a concern for many, it’s important to be aware of other potential side effects associated with Zoloft use. Most side effects are mild and often subside after the first week as the body adjusts to the medication.

Frequently Reported Side Effects

• Nausea
• Diarrhea or constipation
• Headache
• Dry mouth
• Insomnia or drowsiness
• Dizziness
• Fatigue
• Changes in appetite
• Sexual dysfunction (decreased libido, difficulty achieving orgasm)
• Sweating
• Tremors

Do these side effects occur in everyone taking Zoloft? No, the experience of side effects can vary greatly from person to person. Some individuals may experience few or no side effects, while others might find certain side effects more pronounced.

Strategies for Managing Weight While Taking Zoloft

If you’re concerned about potential weight gain while taking Zoloft, there are several strategies you can employ to maintain a healthy weight:

1. Balanced Diet

Focus on consuming a well-balanced diet rich in fruits, vegetables, lean proteins, and whole grains. Be mindful of portion sizes and try to limit intake of high-calorie, processed foods.

2. Regular Exercise

Engage in regular physical activity, aiming for at least 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous-intensity aerobic exercise per week, as recommended by health authorities.

3. Mindful Eating

Practice mindful eating techniques to become more aware of your hunger cues and eating habits. This can help prevent overeating and emotional eating.

4. Stay Hydrated

Drink plenty of water throughout the day. Sometimes, thirst can be mistaken for hunger, leading to unnecessary snacking.

5. Regular Monitoring

Keep track of your weight and body measurements regularly. This can help you identify any significant changes early on and adjust your lifestyle accordingly.

6. Consult Your Healthcare Provider

If you’re experiencing significant weight gain, discuss your concerns with your healthcare provider. They may be able to adjust your medication or suggest alternative treatments.

Can these strategies completely prevent weight gain while on Zoloft? While these approaches can certainly help manage weight, individual responses to the medication may vary. It’s important to work closely with your healthcare provider to find the best approach for your specific situation.

Other SSRIs and Their Impact on Weight

Zoloft is not the only SSRI associated with potential weight changes. Other commonly prescribed SSRIs have also been linked to weight fluctuations:

Citalopram (Celexa)

Like Zoloft, Celexa has been associated with both weight loss in the short term and potential weight gain with long-term use.

Fluoxetine (Prozac)

Prozac is often associated with initial weight loss, but some patients may experience weight gain over time.

Paroxetine (Paxil)

Among SSRIs, Paxil has been most frequently associated with weight gain. Studies suggest that weight gain is more common with paroxetine compared to sertraline (Zoloft) or fluoxetine (Prozac).

Are all SSRIs equally likely to cause weight gain? No, the likelihood and extent of weight gain can vary between different SSRIs. Some medications may be more prone to causing weight changes than others.

The Importance of Medication Adherence

Despite concerns about weight gain or other side effects, it’s crucial to emphasize the importance of medication adherence when prescribed antidepressants like Zoloft.

Risks of Abrupt Discontinuation

Suddenly stopping Zoloft or other SSRIs can lead to discontinuation syndrome, which may include symptoms such as:

• Dizziness
• Nausea
• Flu-like symptoms
• Sensory disturbances
• Anxiety or agitation

Balancing Benefits and Side Effects

When considering the potential side effects of Zoloft, including weight gain, it’s important to weigh these against the benefits of treatment. For many individuals, the positive impact on mental health and overall quality of life outweighs the potential for weight gain.

How can patients best navigate concerns about side effects? Open communication with your healthcare provider is key. If you’re experiencing troublesome side effects or have concerns about your medication, discuss these with your doctor. They can help you weigh the pros and cons and potentially adjust your treatment plan if necessary.

When to Consult Your Doctor

While some side effects of Zoloft are common and may resolve on their own, there are situations where it’s important to seek medical advice:

Severe or Persistent Side Effects

If you experience severe side effects or if mild side effects persist beyond the initial adjustment period (usually a few weeks), consult your healthcare provider.

Significant Weight Changes

If you notice substantial weight gain or loss while taking Zoloft, discuss this with your doctor. They may want to reassess your treatment plan or provide additional guidance on weight management.

Worsening Symptoms

If your depression or anxiety symptoms worsen, or if you experience new symptoms such as increased agitation or suicidal thoughts, seek immediate medical attention.

Pregnancy or Breastfeeding

If you become pregnant or plan to breastfeed while taking Zoloft, consult your doctor to discuss the potential risks and benefits.

When is it appropriate to consider changing medications? If side effects are significantly impacting your quality of life or if the medication isn’t effectively managing your symptoms, your doctor may consider adjusting your dosage or switching to a different antidepressant.

In conclusion, while weight gain is a potential side effect of Zoloft and other SSRIs, it’s not an inevitable outcome for all patients. By understanding the potential effects of the medication, implementing healthy lifestyle strategies, and maintaining open communication with your healthcare provider, you can work towards managing your mental health while minimizing unwanted side effects. Remember, the goal of antidepressant treatment is to improve your overall quality of life, and finding the right balance may require some patience and adjustment.

Zoloft Weight Gain: What You Need To Know

More Americans are talking to their doctors about mental health and getting help. From 2009-2018, the number of U.S. adults taking a prescription antidepressant increased from 10.6% to 13.8%.

While antidepressants can alleviate symptoms of depression and anxiety, they may also cause unwanted side effects. In some patients, this can include weight gain.

Zoloft is a popular antidepressant prescribed for depression.

If you’ve been prescribed this medication or its generic version, sertraline, you may have experienced an improvement in your mood, sleep, and energy levels.

Your appetite might also have increased.

Along with these changes, you may begin to notice you have put on a little weight.

This is unfortunately a possible side effect of many antidepressant medications.

Knowing what to expect can help you manage your symptoms and create healthy lifestyle changes while you are on Zoloft.

In this article, I’ll explain more about why you may gain weight while taking Zoloft or another antidepressant.

I’ll also talk about the other side effects of this medication.

I’ll provide some ways to manage your weight while taking Zoloft, list a few precautions, and tell you when to talk to your doctor.

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Zoloft Weight Gain

If you have been dealing with depression, anxiety, panic attacks, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), or social anxiety disorder (social phobia), your doctor may prescribe you Zoloft to treat your symptoms.

Zoloft is a brand name for sertraline hydrochloride. It is a type of antidepressant called a selective serotonin reuptake inhibitor, or SSRI.

SSRIs work by boosting the serotonin levels in your brain.

Serotonin is a neurotransmitter, a molecule used by your nervous system to carry messages between neurons within the brain and between the brain and the rest of the body’s nervous system.

Under normal circumstances, serotonin conveys a message to a cell receptor, and then excess serotonin molecules are reabsorbed back into the body to be recycled.

When someone takes an SSRI, the medication inhibits the “reuptake” process, increasing the brain’s level of serotonin and giving it more opportunities to communicate. 

Serotonin helps humans think, learn, and remember.

It also helps stabilize mood, balance emotions, regulate appetite, and improve sleep, among other things. Healthcare clinicians aren’t sure whether low levels of serotonin cause major depression and other mental illnesses or vice versa.

We do know that using medications and other treatments to boost and rebalance serotonin levels can positively impact a patient’s mental well-being and quality of life.

Zoloft was first approved for medical use in 1991 by the U.S. Food and Drug Administration (FDA).

It is only available by prescription.

Sertraline is taken orally, in pill or concentrated liquid forms, once a day in the morning or evening.

If it is being used to treat premenstrual dysphoric disorder (PDD), the dose may be prescribed once a day, either every day of the month or on certain days of the month.

Why antidepressants cause weight gain

Serotonin not only regulates your mood and anxiety, but is also involved in control of your appetite.

Consequently, when taking antidepressants, you may develop increased cravings for carbohydrate-rich foods, such as bread, pasta, and desserts.

This can cause weight gain if not monitored and balanced with an active lifestyle.

Experts are not certain what specifically causes weight gain when taking SSRIs.

One hypothesis is that the drugs trigger changes in your metabolism due to the fluctuation in serotonin.

It’s also possible that you may have been eating less when you were depressed and as you start to feel better, your appetite may return.  

Not everyone gains weight while taking an SSRI.

The medications can affect patients in different ways.

Some people put on weight while taking their medication; some lose their appetite or lose weight instead. 

Other common SSRIs that cause weight gain

Most SSRIs have been associated with weight loss when used in the short term.

However, long-term use can result in weight gain.

Other common SSRIs that can cause weight gain include:

• Citalopram (Celexa)
• Fluoxetine (Prozac)
• Paroxetine (Brisdelle, Paxil, Pexeva)

While weight gain has been linked to all of these antidepressants, studies have found that some drugs are more susceptible than others.

There are more cases of weight gain with paroxetine than with sertraline or fluoxetine.

Zoloft Side Effects 

Typically, mild side effects of Zoloft will taper off after the first week as your body gets used to the medication. Some common side effects include:

• Constipation
• Decreased sex drive
• Nervousness
• Restlessness
• Diarrhea
• Headache
• Dizziness
• Drowsiness
• Dry mouth
• Excessive sweating
• Insomnia 
• Loss of appetite
• Nausea
• Upset stomach

More serious side effects require medical attention.

These include:

• Suicidal thoughts or actions
• Seizures or convulsions
• Symptoms of serotonin syndrome
• Difficulty breathing
• Fast, irregular heartbeat
• Skin rash or hives
• Swelling of the face, lips, tongue, or throat
• Black or bloody stools
• Shaking
• Unusual weight loss
• Vision changes or blurred vision
• Vomiting 

Managing Your Weight While on SSRIs

You can manage your weight while on SSRIs by being conscious of your daily diet, increasing physical activity, trying a limited daily window for eating, and getting adequate sleep. 

Watching what you eat

SSRIs can increase appetite.

You may feel strong cravings for foods rich in carbohydrates.

Be mindful of what you are eating when on Zoloft. Simply paying attention to what you’re eating—on purpose, and without judging yourself—can often lead people to maintain a healthy weight.

This is called “mindful eating. ” Though it’s based on practices from Zen Buddhism, you don’t have to meditate to eat mindfully.

Try eating while sitting down, and have meals without your phone or the television screen in front of you.

These simple acts will increase how mindful you are of what you’re eating, and why.

Increase activity 

After taking Zoloft for a few weeks, you may notice a greater interest in activities.

Suddenly, you may find yourself feeling inspired to go on a run or join a fitness class.

Use this to your advantage.

Try to include 30 minutes of physical activity about five times a week.

Intermittent fasting

Intermittent fasting is a strategy where people reduce the number of hours each day during which they eat, setting a “window” for taking in their daily calories.

Some people fast for 12 hours, eating all their meals in the other 12 hours.

Others fast for 16 or even 20 hours.

Other types of intermittent fasting alternate lower-calorie days with regular eating—one popular form is “5:2,” in which people eat significantly less for two days per week.

Intermittent fasting usually results in fewer calories consumed overall, which can lead to weight loss.

Studies have also found that restricting the eating “window” can increase insulin sensitivity in certain patients, which may help with weight loss.

Talk to your doctor before starting any diet regimen to make sure it’s safe for you.

Quality sleep

Many studies have shown a connection between sleep and obesity.

In one study, people who slept five hours per night were 15% more likely to be obese than those who slept seven or more hours per night.

You can improve your sleep by creating a bedtime routine that primes your body for sleep.

Try to go to bed at the same time each day.

Shut off distractions, such as screens, at least an hour before bed.

And give yourself enough time to get to sleep. 

Precautions and Warnings 

Before taking Zoloft, tell your doctor if you are allergic to it or have any other known allergies.

Tell your doctor about any other medications you are taking, including over-the-counter medications and supplements, to avoid negative drug interactions.

There are several SSRIs that work effectively in treating depression.

Tell your doctor about your medical history and symptoms so they can prescribe the best one for you.

What to avoid when taking Zoloft

Avoid drinking alcohol when taking sertraline.

When you drink alcohol, your serotonin levels are temporarily spiked.

Mixing this with Zoloft may bring a temporary high, but can cause a worsening of your symptoms of depression and anxiety in the long term.

In some people, it can even cause a higher risk of suicidal behavior.

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When to See a Doctor 

Do not stop taking Zoloft without medical supervision.

Talk with your doctor if you wish to lower your dose or stop the drug.

They will be able to determine the best treatment for you. 

If you are experiencing worsening symptoms while taking Zoloft, talk to your healthcare provider.

Seek medical attention immediately for any of the following serious side effects:

• Suicidal thoughts or tendencies
• Seizures
• Vision changes including blurred vision, eye pain, redness, or swelling
• Manic episodes: unusual risk-taking behavior, rapid speech, extreme happiness, being irritable, and increased energy
• Hallucinations, memory loss, confusion, or headaches
• Shivering
• Sweating
• Vomiting
• Diarrhea
• Accelerated heart rate 

How K Health Can Help

Think you might need a prescription for Zoloft (Sertraline)?

K Health has clinicians standing by 24/7 to evaluate your symptoms and determine if Zoloft is right for you.

Get started with our free assessment, which will tell you in minutes if treatment could be a good fit. If yes, we’ll connect you right to a clinician who can prescribe medication and have it shipped right to your door.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

K Health has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions,
and medical associations. We avoid using tertiary references.

• Antidepressant Use Among Adults: United States, 2015-2018. (2020).
  https://www.cdc.gov/nchs/products/databriefs/db377.htm

• Mindful Eating: The Art of Presence While You Eat. (2017).
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556586/pdf/171.pdf

• Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. (2018).
  https://www.sciencedirect.com/science/article/pii/S1550413118302535

• Association between Reduced Sleep and Weight Gain in Women. (2006).
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496783/

• The Effects of Calorie Restriction in Depression and Potential Mechanisms. (2015).
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790398/

• Long-Term Weight Change after Initiating Second-Generation Antidepressants. (2016).
  https://pubmed.ncbi.nlm.nih.gov/27089374/

• Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. (2018).
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964332/

• Sertraline (marketed as Zoloft) Information. (2015).
  https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/sertraline-marketed-zoloft-information

• Paroxetine—The Antidepressant from Hell? Probably Not, But Caution Required. (2016).
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044489/

Does Zoloft Cause Weight Gain?

If you’re one of the millions of Americans suffering from depression, you may be familiar with the drug Zoloft. Zoloft is a brand name of the antidepressant drug sertraline hydrochloride which is a Selective Serotonin Reuptake Inhibitor or SSRI. An SSRI works by increasing the level of the “feel-good” hormone in the brain (serotonin). Aside from being a popular treatment for depression, Zoloft is also used to treat people who suffer from panic attacks and social anxiety.

Some of the positive effects that could be experienced after taking Zoloft include better sleep, improved mood, more energy, and better appetite. However, there is one unexpected consequence that has been noticed by many people taking the drug – weight gain.

Is your Zoloft prescription making you fat?

Many people confuse Zoloft with popular anti-anxiety meds such as Xanax. However, Xanax belongs to the benzodiazepine class of drugs so it functions differently from Zoloft. One main difference is that Xanax takes effect instantly so you can feel the effect within 1 to 2 hours after taking the drug.

On the other hand, it could take a couple of weeks for Zoloft to take full effect. Unlike benzodiazepines which should only be taken for the shortest amount of time possible (2 to 4 weeks max), Zoloft is intended to be a long-term treatment and can be taken for up to six months.

While taking Zoloft, many users have noticed an increase in their weight. At least 25% of Zoloft users gain at least 10 pounds after taking the drug. According to a study, this is more likely to happen with long-term use of the drug (6 months or more).

So, the answer to the question of whether Zoloft can make you gain weight is YES. It’s possible to gain weight while on Zoloft. One potential reason is that taking Zoloft can restore your appetite. As you start to feel better overall, you might be eating more without you realizing it.

Weight gain can be good news or bad news depending on how you look at it. If you were severely underweight when you were struggling with depression, gaining a few pounds can be an advantage. This only means that your body is recovering and you’re on your way to a healthier weight.

However, this can also be a disadvantage if gaining weight puts you at the risk of being overweight. Being overweight can have many health risks as well. Another side effect of weight gain is it can cause further depression and anxiety. Instead of the Zoloft helping you to get rid of your depression, gaining weight could add to your woes.

Losing the weight caused by antidepressants

If you feel that your weight gain is unhealthy, you have to consult with your doctor. Don’t stop taking Zoloft without professional advice from your doctor because doing so may backfire on your treatment program.

Avoid self-medicating by using weight loss pills or drinks. Even if the weight-loss products are advertised to be herbal or natural, they could interact with the medications that you are taking for your depression. It is also best to avoid taking other drugs and alcohol while on a Zoloft prescription. This is to avoid serious side effects or drug interactions that could take place.

The best way to lose the weight that you gained from taking anti-depressants is to follow a healthy lifestyle. Gaining back your appetite is a good thing but when you eat, concentrate on healthy food and avoid junk food. Instead of empty carbohydrates like sweets, sugar, pastries, and chips, go for fresh fruits and veggies, lean protein, nuts, and healthy carbs.

Drinking a lot of water and staying active can also help you manage your weight. By exercising or engaging in physical activities, you’re also increasing your endorphins that will make you feel much better.

Are you psychologically addicted to Zoloft?

Because there is no instant effect when taking Zoloft, it is not often used as a recreational drug to get high. However, there are long-time users who become psychologically dependent on Zoloft. If you are one of these people and you feel that you are addicted to Zoloft, consult with a professional. It is possible to get off Zoloft safely and cure your depression at the same time with the right treatment program.

If you or a loved one is struggling with substance abuse, help is available.

Contact Morningside Recovery today.

Antidepressant therapy with antidepressants. Lamictal and the problem of drug resistance | Yastrebov D.V.

Introduction
The initial prescription of antidepressants, the effectiveness of which has been proven in clinical studies, involves achieving a drug response rate of 50-75% within 3-4 weeks of therapy. From this it follows that from 25 to 50% of patients fall into a group of heterogeneous conditions, defined as “treatment-resistant depression” [I.M. Anderson et al., 2000; Schatzberg A.F., 2003]. Today there is no generally accepted definition of the phenomenon of drug resistance. For the most part, the use of this term implies the absence of a satisfactory response to treatment. However, the criteria used in clinical trials, which involve a rating system-based assessment of symptom dynamics as a result of therapy (eg, a 50% reduction in the total score of the HAMD1 scale), are of little use in everyday practice. As one of the reasons for this, one can mention that an improvement of this level is often not recognized by the patient as a positive outcome, which is confirmed by the discrepancy between subjective and objective ratings that is often found in clinical studies [A.J. Rush et al., 2006].

The initial prescription of antidepressants, the effectiveness of which has been proven in clinical studies, involves achieving a drug response rate of 50-75% within 3-4 weeks of therapy. From this it follows that from 25 to 50% of patients fall into a group of heterogeneous conditions, defined as “treatment-resistant depression” [I.M. Anderson et al., 2000; Schatzberg A.F., 2003]. Today there is no generally accepted definition of the phenomenon of drug resistance. For the most part, the use of this term implies the absence of a satisfactory response to treatment. However, the criteria used in clinical trials, which involve a rating system-based assessment of symptom dynamics as a result of therapy (eg, a 50% reduction in the total score of the HAMD1 scale), are of little use in everyday practice. As one of the reasons for this, one can mention that an improvement of this level is often not recognized by the patient as a positive outcome, which is confirmed by the discrepancy between subjective and objective ratings that is often found in clinical studies [A.J. Rush et al., 2006].
Other definitions based on the clinical assessment of the condition suggest an estimate of the number of unsuccessful treatments (2 or more). And finally, the third version of the definitions involves the persistence of depressive symptoms in the absence of success in achieving a state of remission as a result of the therapy (it should be noted that in this case the concepts of remission and drug response are combined) – M. R. Nelsen, D.L. Dunner, 1993; M.E. Thase, P.T. Ninan, 2002.
Any of the listed approaches for determining drug resistance is justified only for patients for whom there were no diagnostic inconsistencies and for whom adequate therapy was initially prescribed. In these cases, one speaks of the so-called “true” resistance. However, there are other options in which the achieved drug response against the doctor’s expectations can be assessed as insufficient. Among them can be named: an error in the choice of an antidepressant or its dosage; poor tolerance, which makes it impossible to use a specific drug in the appropriate dose, violations of compliance, and a number of others (Fig. 1). It is obvious that in these cases, sometimes defined as “pseudo-resistance” or “relative resistance”, medical tactics are fundamentally different and should be aimed at overcoming or eliminating factors that interfere with the achievement of a drug response [H.E. Lehmann, 1974].
After eliminating the signs that allow attributing the lack of a drug response to the account of “pseudo-resistance”, the question arises of determining the “true” (absolute) resistance [D. Bird et al., 2002]. In contrast to the previously existing ideas about drug resistance, as a phenomenon of the atomic order, M. Thase and A. Rush (1997) proposed a dynamic multi-stage system for assessing therapy-resistant depression, which is currently widely used. This typology reflects the authors’ idea of ​​drug resistance as a stage concept that requires comparison of the entire set of previous therapeutic measures that did not lead to an improvement in the condition (Table 1).
More complex is the taxonomically organized European staged method for assessing drug resistance, partially echoing the approach of M. Thase and A. Rush. Each of the stages of resistance, instead of a serial number, has its own definition with the designation of groups of drugs and the terms of their therapy that did not lead to an improvement in the condition (Table 2).
Variants of depressions,
therapy resistant
The issue of determining the clinical subtype of depression (psychotic, atypical, seasonal) is an important component in the management of this group of patients, since such differences may determine sensitivity to a particular therapy option. In addition, resistance to therapy may be due to an erroneous diagnosis with the definition of a unipolar variant of a depressive disorder in a patient with an undiagnosed bipolar course. Due to the fact that depressive phases in patients with bipolar disorder are clinically detected more often (including due to the greater attendance of patients with depressive symptoms), it is expected that up to half of patients with bipolar disorder can receive treatment according to therapeutic algorithms developed for unipolar depression. [S.N. Ghaemi et al., 1999]. As will be shown below, the question of the correct diagnosis of bipolar disorder is key in the appointment of therapy.
Coping methods
drug resistance
Identification of a case of drug resistance dictates to the doctor the need to change the tactics of managing the patient. At the first stage, the choice is made between two main options: changing the antidepressant or prescribing an additional drug to “enhance” the antidepressant effect of the main drug. Let’s take a closer look at each of them.
Changing Therapy
Changing the drug is preferable in the event of a complete lack of response to therapy or in the presence of side effects requiring the withdrawal of the originally prescribed antidepressant. Despite the apparent obviousness of the fact that the change of an antidepressant that turned out to be ineffective should imply the choice of a “second-line” drug with a fundamentally different mechanism of action, there are separate data arguing the expediency of switching to a more potent drug of the same group. In particular, for the most commonly prescribed antidepressants – selective serotonin reuptake inhibitors (SSRIs), it has been shown that the change of less potent drugs (fluoxetine, fluvoxamine, citalopram) that did not improve the symptoms of depression to more potent ones (paroxetine, sertraline) gives a percentage of improvements similar to selective ones. serotonin and norepinephrine reuptake inhibitors (venlafaxine) and selective norepinephrine and dopamine reuptake inhibitors (bupropion) up to 30% of cases. At the same time, the number of cases of early discontinuation of therapy due to developed side effects for “double-acting” drugs is 25% higher than for drugs of the SSRI group. Thus, the assumption that the lack of sensitivity of depressive symptoms to the initially prescribed antidepressant indicates the ineffectiveness of the entire class of drugs with a similar mechanism of action has not been confirmed to date [A.J. Rush et al., 2006]. These data, presented in the form of practical recommendations, show that when changing therapy, it is justified to choose a drug not with the largest number of cumulative mechanisms of action, but with the maximum potential in relation to the leading neurotransmitter system (for SSRIs, this is paroxetine (Paxil) and sertraline). At the same time, certain arguments can be given that do not allow defining this tactic as the main one. In particular, an increase in drug potential automatically means a decrease in tolerability. Thus, in patients who notice the occurrence of certain side effects even during first-line therapy, tactics aimed at enhancing the potential of the drug can lead to worse tolerability and a decrease in the level of drug compliance [Thase M. E., Rush A.J., 1997].
Antidepressant withdrawal policy
Discontinuation of drug antidepressant therapy (AD-therapy) may be accompanied by the occurrence of certain disorders, which are currently accepted to be classified as part of the “anti-adhesion discontinuation syndrome” (AD-AD cessation syndrome).
In earlier studies, the terms “AD withdrawal reaction” and “AD withdrawal syndrome” were more often used to denote pathological symptoms associated with antidepressant (AD) withdrawal [Rotschild, 1995; Dilsaver, 1984; Garner, 1993], which were later changed to emphasize the difference between these disorders and classical withdrawal, which already “reserved” these concepts for itself. However, until now, uncertainty remains in the terminological attribution of the same clinical manifestations, reflecting the opinion of a particular author about the advisability of considering them as withdrawal symptoms [Haddad, 2005].
Early descriptions of SPP AD appeared already in the course of clinical trials of the first ADs (imipramine) [Mann, 1959]. Subsequently, reports of similar disorders were given for almost all groups of AD: other tricyclic antidepressants (TCAs), MAO inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other modern antidepressants [ Hadad, 2004]. It was revealed that the features and severity of SPP BP vary both in relation to different groups of drugs, and for representatives within the same class.
Despite the fact that usually SPP AD manifests itself within a few days after stopping the use of AD or reducing the dosage of the drug and is characterized by a short duration and relative mildness of manifestations, correct recognition if they occur is important, because. these conditions are associated with certain disturbances in daily activities, causing a marked decrease in performance, and their occurrence in a patient unaware of this possibility can lead to serious violations of drug compliance. Also, in some cases, SPP BP can take on a rather pronounced character, requiring hospitalization of the patient [Warner, 2006].
As the main measure to prevent the occurrence of SPP AD or minimize its manifestations, most authors declare the need to follow the prescribed regimen of taking the drug with the elimination of possible interruptions. If it is necessary to cancel blood pressure, it is advisable to follow the method of gradual dose reduction, taking into account the pharmacokinetic properties of a particular drug. The therapeutic value of the last recommendation, in our opinion, however, needs additional verification. According to the data of comparative studies, the gradual abolition of blood pressure allows to achieve an approximately two-fold decrease in the severity of SPP AD compared with one-stage [Van Geffen, 2005]. However, there are other data that show that the gradual withdrawal of the drug rather “blurs” the “rebound” symptoms throughout the entire period of withdrawal. If the manifestations of SPP BP are mild, this technique really makes it possible to additionally “smooth out” them, however, with a greater severity of violations, such tactics of “delaying” may be inappropriate [Yastrebov, 2007]. In addition, the result of gradual withdrawal does not guarantee an asymptomatic outcome of AD withdrawal.
According to various sources, up to 50% of patients diagnosed with SPP AD discontinued the drug gradually [Barr, 1994; Pacheco, 169]. Among the factors associated with an increased risk of developing SPP AD, we can name episodes of reactions to the abolition of AD that have already been noted in the anamnesis. In this case, the risk of developing SPP BP increases to 75% [Black, 2000]. For such patients, when canceling AD, gradual withdrawal over 4–8 weeks is desirable, possibly under the “cover” of a short course of replacement therapy, which can be tranquilizers or AD with a different mechanism of action than the drug being withdrawn. These drugs, on the one hand, stop SPP BP, and on the other hand, allow the corresponding receptor subsystems (but not the concentration of the corresponding neurotransmitter) to return to the “pre-therapeutic” state (for example, when paroxetine is canceled – mirtazapine), which in most cases allows you to “cover up” the manifestations reactive symptomatology throughout its course up to complete regression [Warner, 2006].
Combination therapy
In the event that a certain positive shift in the clinical picture of depression is recorded, which, however, indicates only a partial response to therapy, and at the same time the tolerability of the initially prescribed antidepressant is assessed as satisfactory, it is proposed to use combination therapy with the addition of either another antidepressant (“dual therapy”). ”), or a drug of another class that enhances the effect of the main antidepressant (enhanced therapy). There are some differences between these two combination therapy options.
“Dual” therapy involves the addition of a second antidepressant to an existing monotherapy. At the same time, unlike the procedure for changing an antidepressant, its mechanism of action, if possible, should not overlap with that of the “primary” drug. An example is the combination of a selective serotonin reuptake inhibitor (paroxetine, sertraline, citalopram) or a selective serotonin and norepinephrine reuptake inhibitor with a drug such as mirtazapine. However, this tactic has not been widely adopted for a variety of reasons. The main one is that this approach, despite the simplicity of its definition, is largely based on empirical experience and is difficult to rationally evaluate the effectiveness and formalize the assignment algorithm. To date, there are no comparable data on the effectiveness of various combinations of antidepressants; at the same time, the number of side effects, due to which patients stop treatment, increases significantly. Separately, it is necessary to specify the special care required in these cases in the choice of drugs to exclude undesirable drug interactions.
An enhanced version of combination therapy involves the appointment of an antidepressant, coupled with one of the antipsychotics, or with drugs from the group of mood stabilizers. The latter include lithium salts, carbamazepine, salts of valproic acid and lamotrigine (Table 3).
Limitations in the use of antidepressants
The choice of drugs for antidepressant therapy requires mandatory consideration of the characteristics of the clinical picture of an affective disease and its dynamics in general. So, R. El–Mallakh and A. Karippot (2006) indicate that the presence of a history of signs of a bipolar course makes the appointment of antidepressants alone undesirable due to the possibility of affect inversion, cycle acceleration and the appearance of prolonged irritable dysphoria.
Thus, it is suggested that antidepressant monotherapy is undesirable in patients with depression as part of bipolar disorder due to the possible worsening of the course of bipolar disorder [C.B. Nemeroff, 2001]. Official guidelines published by the American Psychiatric Association [APA Practice Guidelines, 2002] also recommend that antidepressants should not be used as monotherapy in these patients at all initially. Instead, a one-time appointment of at least combination therapy is proposed; it is recommended to use lithium salts or Lamictal (lamotrigine) along with antidepressants as first-line agents at the stage of active therapy. These recommendations are based on recent studies of depression in bipolar disorder defined as resistant to prior therapy (stage II resistance). It has been shown that the appointment of such patients with mood stabilizers (Lamictal (lamotrigine) at doses up to 150-250 mg per day) for combination with antidepressants can significantly increase the level of drug response in comparison with atypical antipsychotics (risperidone) and reduce the likelihood of relapse within a year (with 5% for risperidone to 24% for Lamictal (lamotrigine)) [A. A. Nierenberg et al., 2006].
Separate attention should be paid to the possibility of using drugs that do not belong to the class of antidepressants for monotherapy of depression in bipolar disorder. Existing data confirm the possibility of using some mood stabilizers and atypical antipsychotics in this capacity (Table 4) [K. Fountoulakis et al., 2007].
It must be noted that the appointment of some of the above drugs for long-term therapy (atypical antipsychotics, especially olanzapine), despite proven effectiveness, may be undesirable due to their inherent undesirable side effects, mainly manifested with long-term use (weight gain, metabolic disorders) .
Long-term prophylactic monotherapy with lamotrigine for bipolar depression
Experience with long-term use of Lamictal has shown that this drug is equally effective in bipolar I and II disorders [Geddes, 2009]. The advantages of Lamictal, which justify its use at the stage of long-term preventive therapy, are: the effect on the residual manifestations of depression, the absence of rebound symptoms upon withdrawal, and the minimal presence of side effects [Calabrese, 2008]. Of particular value to the drug is the absence of the ability to cause weight gain with long-term use, which may justify the need to transfer patients with a tendency to obesity from other drugs (including lithium) to it [Bowden, 2006].
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¹ HAMD: Hamilton Depression Rating Scale

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