What are SSRIs and how do they work. Which conditions can SSRIs treat effectively. What are the common side effects of SSRI medications. How long does it take for SSRIs to start working. What should patients know before starting SSRI treatment.

Understanding SSRIs: Mechanism of Action and Therapeutic Uses

Selective Serotonin Reuptake Inhibitors (SSRIs) are a widely prescribed class of antidepressant medications. These drugs work by increasing the levels of serotonin, a neurotransmitter associated with mood regulation, in the brain. SSRIs accomplish this by blocking the reabsorption (reuptake) of serotonin into neurons, allowing more serotonin to remain available for transmitting signals between brain cells.

While the exact relationship between serotonin levels and depression is complex, increasing serotonin availability appears to alleviate symptoms in many patients. SSRIs are often the first-line treatment for depression due to their generally favorable side effect profile compared to other antidepressants.

Primary Uses of SSRIs

• Major depressive disorder
• Generalized anxiety disorder (GAD)
• Obsessive-compulsive disorder (OCD)
• Panic disorder
• Social anxiety disorder
• Post-traumatic stress disorder (PTSD)
• Bulimia nervosa

SSRIs may also be prescribed off-label for conditions such as premenstrual dysphoric disorder (PMDD), fibromyalgia, and irritable bowel syndrome (IBS). In some cases, they are used to manage chronic pain conditions.

SSRI Medications: Types and Characteristics

There are several SSRI medications available by prescription in many countries. While they share the same basic mechanism of action, individual SSRIs can differ in their specific chemical structures, half-lives, and potential for drug interactions.

Commonly Prescribed SSRIs

1. Fluoxetine (Prozac)
2. Sertraline (Zoloft)
3. Paroxetine (Paxil)
4. Citalopram (Celexa)
5. Escitalopram (Lexapro)
6. Fluvoxamine (Luvox)
7. Vortioxetine (Trintellix)
8. Dapoxetine (Priligy) – primarily used for premature ejaculation

Why are there multiple SSRIs if they all work similarly? Different patients may respond better to one SSRI than another due to individual variations in metabolism, brain chemistry, and genetic factors. Additionally, the slight differences between SSRIs can affect their side effect profiles and potential drug interactions.

Initiating SSRI Treatment: Dosage and Duration Considerations

When prescribing SSRIs, healthcare providers typically start with the lowest effective dose to minimize side effects. The initial dosage may be gradually increased over several weeks if needed to achieve the desired therapeutic effect.

How long does it take for SSRIs to work? Unlike some medications that provide immediate relief, SSRIs generally require 2-4 weeks of consistent use before patients notice significant improvements in mood and other symptoms. This delay is due to the time needed for the brain to adapt to the increased serotonin levels and make corresponding changes in neural pathways.

Patients are usually advised to continue SSRI treatment for at least 6 months after symptom improvement to reduce the risk of relapse. In some cases, particularly for individuals with recurrent depression, long-term or indefinite use may be recommended.

Factors Affecting SSRI Efficacy

• Consistent daily administration
• Adequate dosage
• Patient compliance with treatment
• Individual variations in metabolism and brain chemistry
• Concurrent use of other medications or substances

Navigating SSRI Side Effects: Common Issues and Management Strategies

While SSRIs are generally well-tolerated, they can cause side effects, especially during the initial weeks of treatment. Many side effects are mild and tend to improve as the body adjusts to the medication.

Frequently Reported SSRI Side Effects

• Nausea and gastrointestinal disturbances
• Headache
• Sleep disturbances (insomnia or excessive sleepiness)
• Sexual dysfunction (decreased libido, difficulty reaching orgasm)
• Dry mouth
• Increased sweating
• Jitteriness or restlessness
• Weight changes

Can SSRI side effects be managed effectively? Many side effects can be mitigated through strategies such as taking the medication with food to reduce nausea, adjusting the timing of doses to minimize sleep disturbances, or slowly tapering up the dose. In some cases, switching to a different SSRI or adjusting the dosage may help alleviate persistent side effects.

SSRI Interactions: Medications and Substances to Avoid

SSRIs can interact with various medications and substances, potentially leading to adverse effects or reduced efficacy. It’s crucial for patients to inform their healthcare providers about all medications, supplements, and recreational substances they use.

Potential SSRI Interactions

• Monoamine oxidase inhibitors (MAOIs)
• Other antidepressants (e.g., tricyclic antidepressants)
• Certain pain medications (e.g., tramadol)
• Some migraine medications (triptans)
• St. John’s Wort (an herbal supplement)
• Alcohol and recreational drugs

Why is it important to avoid certain substances while taking SSRIs? Some interactions can lead to dangerous increases in serotonin levels, potentially causing serotonin syndrome, a potentially life-threatening condition. Other interactions may increase the risk of bleeding or alter the metabolism of the SSRI, affecting its efficacy.

Special Considerations: SSRIs in Specific Populations

While SSRIs are generally safe for most adults, certain populations require special consideration when it comes to SSRI use.

Pregnancy and Breastfeeding

The use of SSRIs during pregnancy and breastfeeding is a complex decision that requires careful weighing of potential risks and benefits. Some SSRIs have been associated with a slight increase in the risk of certain birth defects, particularly when used in the first trimester. However, untreated depression during pregnancy also carries risks for both mother and baby.

Are there safe options for treating depression during pregnancy? Some SSRIs, such as sertraline and citalopram, are considered to have a better safety profile during pregnancy. The decision to use SSRIs during pregnancy or breastfeeding should be made in consultation with a healthcare provider, considering the severity of depression and potential alternatives.

Children and Adolescents

The use of SSRIs in individuals under 18 is approached with caution due to concerns about an increased risk of suicidal thoughts and behaviors in this age group. However, in cases of severe depression or anxiety, the benefits of SSRI treatment may outweigh the risks.

Which SSRIs are approved for use in children and adolescents? In many countries, fluoxetine is approved for use in children aged 8 and older for depression, and several SSRIs are approved for OCD in pediatric populations. Close monitoring is essential when SSRIs are prescribed to young people, especially during the initial weeks of treatment.

Elderly Patients

Older adults may be more sensitive to the effects of SSRIs and may be at increased risk for certain side effects, such as falls and bleeding. Lower starting doses and careful monitoring are often recommended for elderly patients.

Discontinuing SSRIs: Tapering and Withdrawal Considerations

Abruptly stopping SSRI treatment can lead to discontinuation syndrome, a collection of symptoms that can occur as the body adjusts to the absence of the medication.

Common SSRI Discontinuation Symptoms

• Dizziness
• Flu-like symptoms
• Irritability
• Electric shock sensations (brain zaps)
• Anxiety or agitation
• Sleep disturbances

How can SSRI discontinuation syndrome be prevented? Gradually tapering the dose under medical supervision is the best way to minimize withdrawal symptoms. The tapering schedule depends on factors such as the specific SSRI, the duration of treatment, and individual patient characteristics.

It’s important to note that discontinuation symptoms are not indicative of addiction. SSRIs are not considered addictive in the way that substances like opioids or benzodiazepines can be. However, the body does adapt to their presence, necessitating a gradual reduction to avoid discomfort.

Combining SSRIs with Other Treatment Modalities

While SSRIs can be effective on their own, they are often most beneficial when combined with other forms of treatment, particularly psychotherapy.

Psychotherapy and SSRIs

Cognitive Behavioral Therapy (CBT) is frequently recommended alongside SSRI treatment for depression and anxiety disorders. The combination of medication and therapy can be more effective than either treatment alone for many patients.

How do SSRIs enhance the effects of psychotherapy? By alleviating severe symptoms, SSRIs can make patients more receptive to therapeutic interventions. This synergistic effect often leads to better long-term outcomes and a reduced risk of relapse.

Lifestyle Modifications

In addition to medication and therapy, lifestyle changes can significantly enhance the effectiveness of SSRI treatment:

• Regular exercise
• Healthy sleep habits
• Balanced nutrition
• Stress reduction techniques (e.g., mindfulness meditation)
• Social support

These lifestyle factors can help regulate mood, improve overall well-being, and potentially allow for lower SSRI doses in some cases.

SSRIs represent a significant advance in the treatment of depression and related disorders. While they are not a panacea and come with potential side effects and considerations, they have helped millions of people worldwide manage their mental health conditions more effectively. As with any medication, the decision to start SSRI treatment should be made in consultation with a qualified healthcare provider, taking into account individual circumstances, potential risks and benefits, and alternative treatment options.

Overview – SSRI antidepressants – NHS

Selective serotonin reuptake inhibitors (SSRIs) are a widely used type of antidepressant.

They’re mainly prescribed to treat depression, particularly persistent or severe cases, and are often used in combination with a talking therapy such as cognitive behavioural therapy (CBT).

SSRIs are usually the first choice medicine for depression because they generally have fewer side effects than most other types of antidepressant.

As well as depression, SSRIs can be used to treat a number of other mental health conditions, including:

• generalised anxiety disorder (GAD)
• obsessive compulsive disorder (OCD)
• panic disorder
• severe phobias, such as agoraphobia and social phobia
• bulimia
• post-traumatic stress disorder (PTSD)

SSRIs can sometimes be used to treat other conditions, such as premenstrual syndrome (PMS), fibromyalgia and irritable bowel syndrome (IBS). Occasionally, they may also be prescribed to treat pain.

How SSRIs work

It’s thought that SSRIs work by increasing serotonin levels in the brain.

Serotonin is a neurotransmitter (a messenger chemical that carries signals between nerve cells in the brain). It’s thought to have a good influence on mood, emotion and sleep.

After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as “reuptake”). SSRIs work by blocking (“inhibiting”) reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells.

It would be too simplistic to say that depression and related mental health conditions are caused by low serotonin levels, but a rise in serotonin levels can improve symptoms and make people more responsive to other types of treatment, such as CBT.

Doses and duration of treatment

SSRIs are usually taken in tablet form. When they’re prescribed, you’ll start on the lowest possible dose thought necessary to improve your symptoms.

SSRIs usually need to be taken for 2 to 4 weeks before the benefit is felt. You may experience mild side effects early on, but it’s important that you don’t stop taking the medicine. These effects will usually wear off quickly.

If you take an SSRI for 4 to 6 weeks without feeling any benefit, speak to your GP or mental health specialist. They may recommend increasing your dose or trying an alternative antidepressant.

A course of treatment usually continues for at least 6 months after you feel better, although longer courses are sometimes recommended and some people with recurrent problems may be advised to take them indefinitely.

Things to consider

SSRIs aren’t suitable for everyone. They’re not usually recommended if you’re pregnant, breastfeeding or under 18, because there’s an increased risk of serious side effects. However, exceptions can be made if the benefits of treatment are thought to outweigh the risks.

SSRIs also need to be used with caution if you have certain underlying health problems, including diabetes, epilepsy and kidney disease.

Some SSRIs can react unpredictably with other medicines, including some over-the-counter painkillers and herbal remedies, such as St John’s wort. Always read the information leaflet that comes with your SSRI medicine to check if there are any medicines you need to avoid.

Side effects

Most people will only experience a few mild side effects when taking SSRIs. These can be troublesome at first, but they’ll generally improve with time.

Common side effects of SSRIs can include:

• feeling agitated, shaky or anxious
• diarrhoea and feeling or being sick
• dizziness
• blurred vision
• loss of libido (reduced sex drive)
• difficulty achieving orgasm during sex or masturbation
• in men, difficulty obtaining or maintaining an erection (erectile dysfunction)

You’ll usually need to see your doctor every few weeks when you first start taking SSRIs to discuss how well the medicine is working. You can also contact your doctor at any point if you experience any troublesome or persistent side effects.

Types of SSRIs

There are currently 8 SSRIs prescribed in the UK:

• citalopram (Cipramil)
• dapoxetine (Priligy)
• escitalopram (Cipralex)
• fluoxetine (Prozac or Oxactin)
• fluvoxamine (Faverin)
• paroxetine (Seroxat)
• sertraline (Lustral)
• vortioxetine (Brintellix)

Page last reviewed: 8 December 2021

Next review due: 8 December 2024

SSRIs: Uses, Side-Effects, and Cessation

Written by Matthew Hoffman, MD

Medically Reviewed by Jennifer Robinson, MD on May 02, 2023

• How Do SSRIs Work?
• Types of SSRIs
• Side Effects
• How Long Do They Take to Work?
• Stopping Treatment

Everyone feels down from time to time. But for people with depression, the feelings of sadness can be so severe that they interfere with everyday life. It can become hard to function at home or at work, and the feelings can lead to a variety of physical and emotional problems.

However, depression is one of the most treatable mental disorders. Between 80% and 90%of people who have it benefit from treatment. The kind of management you need depends on your specific situation, but for some people, medication can be very helpful.

That’s because brain chemistry may contribute to the condition, so taking antidepressants can actually change your brain chemistry and help you feel better.

The most common antidepressants are called selective serotonin reuptake inhibitors (SSRIs). They’re considered relatively safe and cause fewer side effects than other kinds of medications used to treat depression.

SSRIs work by enhancing the function of nerve cells in the brain that regulate emotion. Information is communicated between your brain cells with signals. The chemical messengers that deliver these signals are called neurotransmitters. Serotonin is one type of neurotransmitter.

When these brain cells (called neurons) send signals to one another, they release a little bit of a neurotransmitter so that the message can be delivered. They then have to take back the neurotransmitter they released so they can send the next message. This process of replacing the neurotransmitter is called “reuptake.”

If you’re struggling with depression, the areas of your brain that regulate mood and send messages using serotonin might not function properly. SSRIs help make more serotonin available by blocking the reuptake process. This allows serotonin to build up between neurons so messages can be sent correctly. They’re called “selective” serotonin reuptake inhibitors because they specifically target serotonin.

The FDA is in charge of deciding which medications are safe and effective for which reasons. The following SSRIs are approved to treat depression, anxiety, and other mood disorders:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Fluvoxamine 
• Paroxetine (Paxil, Paxil CR)
• Sertraline (Zoloft)
• Vilazodone (Viibryd) 

Most people who use SSRI antidepressants don’t have major problems, but every kind of medical treatment carries some risk. The possible side effects of these antidepressants include:

• Insomnia
• Headaches
• Rash
• Blurred vision
• Drowsiness
• Dry mouth
• Agitation or nervousness
• Feeling dizzy
• Pain in the joints or muscles
• Upset stomach, nausea, or diarrhea
• Reduced sexual desire
• Problems with erection or ejaculation

Some people, especially children and young adults, may be more likely to have suicidal thoughts when they take SSRIs. Studies show that when compared to results from taking a placebo, chances of having suicidal thoughts doubled — from between 1% and 2% to between 2% and 4% — when taking any kind of antidepressant, including an SSRI. If you have thoughts of hurting yourself while taking an SSRI, call 911.

There are also important safety issues to consider about SSRIs. Although it’s rare, if too much serotonin accumulates in your system, you can develop a condition called serotonin syndrome. This happens most often if two different medications that increase serotonin are combined.

SSRIs can also have dangerous interactions with some medicines, both prescription and over-the-counter, including herbs and supplements. Before starting on an SSRI, make sure to tell your doctor all the different kinds of medications and supplements you’re taking.

Since all SSRIs work in a similar way, the side effects tend to be similar no matter what kind you take. But each SSRI has a different chemical makeup, so it’s possible that if you’re having side effects from one, you may not experience as many or any at all if you switch to another.

While some people do have side effects, others do not, and in many cases, the side effects disappear after a few weeks of treatment. It’s important to work with your doctor to find a medication that’s right for you.

Everyone is different when it comes to seeing improvements on SSRIs. But people typically start noticing positive changes after about 4 to 6 weeks of treatment. It can take several months to feel the full effect of the medication.

But if you’re not feeling any improvements after about 6 to 8 weeks, talk to your doctor about trying another treatment or adjusting your dosage.

Even though SSRIs aren’t habit-forming, it can be dangerous to stop them suddenly or miss several doses in a row. Doing this can lead to a condition called discontinuation syndrome that causes withdrawal-like symptoms.

If you do experience discontinuation syndrome, you might start to feel like you have the flu and/or notice symptoms like:

• Nausea
• Dizziness
• Uneasiness
• Fatigue or lethargy

That’s why it’s important to work up to your prescribed dosage slowly with the help of your doctor, and to step down gradually if you agree it’s time to stop.

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Antidepressants: pharmacological group

Drugs specifically for depression appeared in the late 1950s. In 1957, iproniazid was discovered, which became the ancestor of the group of antidepressants – MAO inhibitors, and imipramine, on the basis of which tricyclic antidepressants were obtained.

According to modern concepts, in depressive states, there is a decrease in serotonergic and noradrenergic synaptic transmission. Therefore, the accumulation of serotonin and norepinephrine in the brain caused by them is considered an important link in the mechanism of action of antidepressants. MAO inhibitors block monoamine oxidase, an enzyme that causes oxidative deamination and inactivation of monoamines. Currently, two forms of MAO are known – type A and type B, which differ in the substrates exposed to them. Type A MAO causes mainly the deamination of noradrenaline, adrenaline, dopamine, serotonin, tyramine, and type B MAO causes the deamination of phenylethylamine and some other amines. Allocate inhibition competitive and non-competitive, reversible and irreversible. Substrate specificity can be observed: a predominant effect on the deamination of various monoamines. All this significantly affects the pharmacological and therapeutic properties of various MAO inhibitors. So, iproniazid, nialamide, phenelzine, tranylcypromine irreversibly block MAO type A, and pirlindol, tetrindole, metralindol, eprobemide, moclobemide, etc. have a selective and reversible effect on it.

Tricyclic antidepressants are named because of their characteristic tricyclic structure. The mechanism of their action is associated with inhibition of the reuptake of neurotransmitter monoamines by presynaptic nerve endings, resulting in the accumulation of mediators in the synaptic cleft and activation of synaptic transmission. Tricyclic antidepressants, as a rule, simultaneously reduce the capture of various neurotransmitter amines (norepinephrine, serotonin, dopamine). Recently, antidepressants have been created that block predominantly (selectively) the reuptake of serotonin (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, etc.).

There are also so-called “atypical” antidepressants, which differ from the “typical” ones both in structure and mechanism of action. Preparations of a bi- and four-cyclic structure appeared, in which no pronounced effect was found either on the capture of neurotransmitters or on the activity of MAO (mianserin, etc.).

A common property of all antidepressants is their thymoleptic effect, that is, a positive effect on the affective sphere of the patient, accompanied by an improvement in mood and general mental state. Different antidepressants differ, however, in the amount of pharmacological properties. So, in imipramine and some other antidepressants, the thymoleptic effect is combined with a stimulating one, while in amitriptyline, pipofezin, fluacizine, clomipramine, trimipramine, doxepin, a sedative component is more pronounced. In maprotiline, the antidepressant effect is combined with anxiolytic and sedative. MAO inhibitors (nialamide, eprobemide) have stimulating properties. Pirlindol, removing the symptoms of depression, exhibits nootropic activity, improves “cognitive” (“cognitive”) functions of the central nervous system.

Antidepressants have found application not only in psychiatric practice, but also for the treatment of a number of neurovegetative and somatic diseases, chronic pain syndromes, etc.

The therapeutic effect of antidepressants, both oral and parenteral, develops gradually and usually manifests itself after 3–10 or more days after the start of treatment. This is explained by the fact that the development of the antidepressant effect is associated both with the accumulation of neurotransmitters in the region of nerve endings, and with slowly appearing adaptive changes in the circulation of neurotransmitters and in the sensitivity of brain receptors to them.

From Mania to Depression: Understanding Bipolar Disorder

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