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A Selective Serotonin Reuptake Inhibitor, or SSRI, is a medicinal compound, classed as an antidepressant, and used to treat depression. This group of antidepressants are also used to treat anxiety disorders, some personality disorders and insomnia. When used in reference to medicines, the term 'group' means that each of the drugs in the group is broadly similar to the others in the way that it works. Post traumatic Stress Disorder (PTSD) is an Dead Link Removed, the symptoms of which often include depression and insomnia. As such, SSRI’s are frequently prescribed to patients who suffer with PTSD. Other groups of antidepressants include: monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), and serotonin-norepinephrine reuptake inhibitors (SNRIs)
Mode Of Action
Each nerve cell in the brain relays information from one cell to the next, by way of chemicals called neurotransmitters. Serotonin, is just one of many neurotransmitters (Dopamine and Noradrenaline being others), depending on the cell type. Serotonin is produced in the pineal gland, which lies deep at the center of the human brain, via a unique biochemical conversion process. Tryptophan, which is a building block to proteins combines with tryptophan hydroxylase (an enzyme) to form 5-hydoxytryptamine (5HT), otherwise known as Serotonin.
SSRI medications increase the level of serotonin in the brain cells by blocking the reuptake of serotonin. If a brain cell does not release enough serotonin, the messages can’t be passed between the cells, so the message doesn’t get through. Nerve cells recycle the serotonin by absorbing it back into the cell. SSRI’s block (inhibit) this re-absorption of serotonin, meaning that more is present around the cells, to pass on the information.
SSRI’s work selectively on Serotonin – they do not affect any other neurotransmitters.
Low serotonin levels were believed to be the cause of many cases of mild to severe depression that can lead to symptoms such as anxiety, apathy, fear, feelings of worthlessness, insomnia and fatigue. Research found the connection between serotonin and depression by discovering decreased concentrations of serotonin metabolites in the cerebrospinal fluid and brain tissues of depressed people. However, further reviews of that research has shown flaws with the methodolgy, such as very small sample sizes and uncontrolled variables. Attempts were also made to induce depression by depleting serotonin levels, but these experiments reaped no consistent results. Likewise, researchers found that huge increases in brain serotonin, arrived at by administering high-dose Ltryptophan, were ineffective at relieving depression.
So even whether SSRI's 'work', and if they do why, is constantly under debate.
When comparing an SSRI to a placebo, several studies have shown similar results. Firstly there is a significant effect in both SSRI and placebo treatment compared to no treatment. Several clinical trials found that in mild and moderate depression the effect of SSRI is very small or none compared to placebo, while in very severe depression the effect of SSRI is clinically significant.
List of SSRIs
Drugs in this group include (brand names in brackets):
The main indication for SSRI’s is clinical depression. SSRI’s are effective for treating moderate to severe depression. Ideally patients with moderate to severe depression should be treated with psychological therapy, as well as drug therapy.
Antidepressants of any kind are not generally recommended for mild depression. Psychological therapy should be considered in the first instance. SSRI’s can be considered for mild depression that doesn’t respond to psychological treatments or when the patient has a previous history of moderate to severe depression.
Dosage
The recommended dosage is dependant on the type of SSRI, and the severity of the symptoms. Dosages may be different for different people. It’s important to take the drug as prescribed by the Doctor.
Management
If you are prescribed a Selective Serotonin Reuptake Inhibitor (SSRI), it is important to mention any other medicines that you take, whether prescribed or bought over the counter. Be sure to take the SSRI exactly as prescribed. A Doctor should monitor a patient during the first weeks of taking the drug, to observe any side effects or unusual behaviour. Do not stop taking an SSRI medicine abruptly. This is because you may develop some withdrawal symptoms. The dose is usually gradually reduced before stopping completely at the end of a course of treatment. But don't do this yourself - your doctor will advise on dosage reduction when the time comes. It is best not to stop treatment or change the dose without consulting a doctor.
SSRI’s can take 2-4 weeks to build up their effect to work fully. Some people stop treatment after a week or so thinking it is not helping. It is best to wait for 3-4 weeks before deciding if treatment with an SSRI is helping or not.
If you find that the treatment is helpful after 3-4 weeks, it is usual to continue. A normal course of antidepressants lasts at least six months after symptoms have eased. If you stop the medicine too soon, your symptoms may rapidly return. Some people with recurrent depression are advised to take longer courses of treatment.
There is no best type of SSRI that suits everyone. If the one chosen does not suit, it is sometimes necessary to change the dose, or change the preparation. Your doctor will advise you. Also, if SSRI antidepressants do not help then another type of antidepressant may be advised.
Contraindications
Certain medications react with other medications. If you are taking other drugs, whether prescribed, or bought over the counter, you should always check with your Doctor and pharmacist, that they are safe to take together.
In general SSRI's should not be taken in conjunction with
SSRI's can cause other medicines to reach toxic levels, likewise other medications can increase the toxicity of SSRI's. These type of medications can be taken together, but regular blood tests will be required to ensure that no toxicity occurs. Listing specific medications in these groups for each of the SSRI's is beyond the scope of this article. However, all contraindications and cautionary advice is contained in the leaflet supplied with the medications and any queries can be answered by your Doctor and pharmacist. As with any new medication, if you experience any unusual, or worrying symptoms, then you should seek further medical advice.
Side Effects
Antidepressants may cause mild and often temporary side effects in some people, but they are usually not long–term. However, any unusual reactions or side effects that interfere with normal functioning should be reported to a doctor immediately.
The most common side effects associated with SSRIs include :
Despite the relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that they may have unintentional effects on some people, especially adolescents and young adults. In 2004, the U.S. Food and Drug Administration (FDA) conducted a thorough review of published and unpublished controlled clinical trials of antidepressants that involved nearly 4,400 children and adolescents. The review revealed that 4% of those taking antidepressants thought about or attempted suicide (although no suicides occurred), compared to 2% of those receiving placebos.
This information prompted the FDA, in 2005, to adopt a "black box" warning label on all antidepressant medications to alert the public about the potential increased risk of suicidal thinking or attempts in children and adolescents taking antidepressants. In 2007, the FDA proposed that makers of all antidepressant medications extend the warning to include young adults up through age 24. A "black box" warning is the most serious type of warning on prescription drug labelling.
The warning emphasizes that patients of all ages taking antidepressants should be closely monitored, especially during the initial weeks of treatment. Possible side effects to look for are worsening depression, suicidal thinking or behaviour, or any unusual changes in behaviour such as sleeplessness, agitation, or withdrawal from normal social situations. The warning adds that families and caregivers should also be told of the need for close monitoring and report any changes to the physician.
Serotonin Syndrome
Finally, the FDA has warned that combining the newer SSRI antidepressants with one of the commonly-used "triptan" medications used to treat migraine headaches could cause a life-threatening illness called "serotonin syndrome." A person with serotonin syndrome may be agitated, have hallucinations (see or hear things that are not real), have a high temperature, or have unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs (monoamine oxidase inhibitor), but it can happen with the newer antidepressants as well, if they are mixed with the wrong medications.
Other Considerations
SSRIs are better tolerated and are safer in overdose than other classes of antidepressants and therefore are considered first-line drug therapy for treating depression. Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem.
Clinical Trials
The selective serotonin reuptake inhibitors (SSRIs) are the most studied medications for PTSD, with the largest number of double-blind, placebo-controlled trials. Of the SSRIs, sertraline, paroxetine and fluoxetine have been the most extensively studied. These studies have demonstrated that SSRIs are effective in short-term trials (6-12 weeks). Furthermore, continuation and maintenance treatment for 6-12 months decrease relapse rates. Besides being the most studied and effective drugs for PTSD, SSRIs have a favourable adverse effect profile, making them the first-line treatment for PTSD. If SSRIs are not tolerated or are ineffective, non-SSRIs should be considered.
In 2004, two drugs were approved for treating PTSD by the U.S. Food and Drug Administration (FDA). Both were SSRI’s; Paroxetine and Sertraline. FDA approval is based on multi-center double-blind studies.
Studies with fluoxetine and paroxetine have shown that these medications are both superior to placebo among combat veterans. Many studies with civilians and some studies with combat veterans have provided clear evidence that SSRIs, tricyclic antidepressants, and MOI's are useful in treating chronic PTSD. Rates of clinical remission for patients given fluoxetine and paroxetine are around 40% after 3 months, compared with 4% to 18% for those given placebo.
SSRIs have a broad effect on all symptom clusters as well as on all the individual symptoms of PTSD. SSRIs appear to start to work rapidly in patients with chronic PTSD, with improvements in irritability and anger evident as early as during the first week. In this domain, SSRI therapy has a marked, early, and sustained effect.
Mode Of Action
Each nerve cell in the brain relays information from one cell to the next, by way of chemicals called neurotransmitters. Serotonin, is just one of many neurotransmitters (Dopamine and Noradrenaline being others), depending on the cell type. Serotonin is produced in the pineal gland, which lies deep at the center of the human brain, via a unique biochemical conversion process. Tryptophan, which is a building block to proteins combines with tryptophan hydroxylase (an enzyme) to form 5-hydoxytryptamine (5HT), otherwise known as Serotonin.
SSRI medications increase the level of serotonin in the brain cells by blocking the reuptake of serotonin. If a brain cell does not release enough serotonin, the messages can’t be passed between the cells, so the message doesn’t get through. Nerve cells recycle the serotonin by absorbing it back into the cell. SSRI’s block (inhibit) this re-absorption of serotonin, meaning that more is present around the cells, to pass on the information.
SSRI’s work selectively on Serotonin – they do not affect any other neurotransmitters.
Low serotonin levels were believed to be the cause of many cases of mild to severe depression that can lead to symptoms such as anxiety, apathy, fear, feelings of worthlessness, insomnia and fatigue. Research found the connection between serotonin and depression by discovering decreased concentrations of serotonin metabolites in the cerebrospinal fluid and brain tissues of depressed people. However, further reviews of that research has shown flaws with the methodolgy, such as very small sample sizes and uncontrolled variables. Attempts were also made to induce depression by depleting serotonin levels, but these experiments reaped no consistent results. Likewise, researchers found that huge increases in brain serotonin, arrived at by administering high-dose Ltryptophan, were ineffective at relieving depression.
So even whether SSRI's 'work', and if they do why, is constantly under debate.
When comparing an SSRI to a placebo, several studies have shown similar results. Firstly there is a significant effect in both SSRI and placebo treatment compared to no treatment. Several clinical trials found that in mild and moderate depression the effect of SSRI is very small or none compared to placebo, while in very severe depression the effect of SSRI is clinically significant.
List of SSRIs
Drugs in this group include (brand names in brackets):
- Citalopram (Celexa, Cipramil, Cipram, Recital, Emocal, Dalsan, Sepram, Seropram, Citox)
- Dapoxetine (Priligy)
- Escitalopram Oxalate (Lexapro, Cipralex, Seroplex, Esertia)
- Fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Ladose, Motivest, Fluctin, fluox, Lovan)
- Fluvoxamine (Luvox, Fevarin, Faverin, Favoxil, Movox)
- Paroxetine (Paxil, Seroxat, Sereupin, Aropax, Deroxat, Divarius, Rexetin, Xetanor, Paroxat, Loxamine)
- Sertraline (Zoloft, Lustral, Serlain, Asentra)
The main indication for SSRI’s is clinical depression. SSRI’s are effective for treating moderate to severe depression. Ideally patients with moderate to severe depression should be treated with psychological therapy, as well as drug therapy.
Antidepressants of any kind are not generally recommended for mild depression. Psychological therapy should be considered in the first instance. SSRI’s can be considered for mild depression that doesn’t respond to psychological treatments or when the patient has a previous history of moderate to severe depression.
Dosage
The recommended dosage is dependant on the type of SSRI, and the severity of the symptoms. Dosages may be different for different people. It’s important to take the drug as prescribed by the Doctor.
Management
If you are prescribed a Selective Serotonin Reuptake Inhibitor (SSRI), it is important to mention any other medicines that you take, whether prescribed or bought over the counter. Be sure to take the SSRI exactly as prescribed. A Doctor should monitor a patient during the first weeks of taking the drug, to observe any side effects or unusual behaviour. Do not stop taking an SSRI medicine abruptly. This is because you may develop some withdrawal symptoms. The dose is usually gradually reduced before stopping completely at the end of a course of treatment. But don't do this yourself - your doctor will advise on dosage reduction when the time comes. It is best not to stop treatment or change the dose without consulting a doctor.
SSRI’s can take 2-4 weeks to build up their effect to work fully. Some people stop treatment after a week or so thinking it is not helping. It is best to wait for 3-4 weeks before deciding if treatment with an SSRI is helping or not.
If you find that the treatment is helpful after 3-4 weeks, it is usual to continue. A normal course of antidepressants lasts at least six months after symptoms have eased. If you stop the medicine too soon, your symptoms may rapidly return. Some people with recurrent depression are advised to take longer courses of treatment.
There is no best type of SSRI that suits everyone. If the one chosen does not suit, it is sometimes necessary to change the dose, or change the preparation. Your doctor will advise you. Also, if SSRI antidepressants do not help then another type of antidepressant may be advised.
Contraindications
Certain medications react with other medications. If you are taking other drugs, whether prescribed, or bought over the counter, you should always check with your Doctor and pharmacist, that they are safe to take together.
In general SSRI's should not be taken in conjunction with
- MAOI's (monoamine oxidase inhibitors)
- Pimozide (an antipsychotic diphenylbutylpiperidine derivative).
- Tramadol hydrochloride (or Ultram, Ultracet)
SSRI's can cause other medicines to reach toxic levels, likewise other medications can increase the toxicity of SSRI's. These type of medications can be taken together, but regular blood tests will be required to ensure that no toxicity occurs. Listing specific medications in these groups for each of the SSRI's is beyond the scope of this article. However, all contraindications and cautionary advice is contained in the leaflet supplied with the medications and any queries can be answered by your Doctor and pharmacist. As with any new medication, if you experience any unusual, or worrying symptoms, then you should seek further medical advice.
Side Effects
Antidepressants may cause mild and often temporary side effects in some people, but they are usually not long–term. However, any unusual reactions or side effects that interfere with normal functioning should be reported to a doctor immediately.
The most common side effects associated with SSRIs include :
- Headache–usually temporary and will subside.
- Nausea–temporary and usually short–lived.
- Insomnia and nervousness (trouble falling asleep or waking often during the night)–may occur during the first few weeks but often subside over time or if the dose is reduced.
- Agitation (feeling jittery).
- Sexual problems–both men and women can experience sexual problems including reduced sex drive, erectile dysfunction, delayed ejaculation, or inability to have an orgasm.
Despite the relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that they may have unintentional effects on some people, especially adolescents and young adults. In 2004, the U.S. Food and Drug Administration (FDA) conducted a thorough review of published and unpublished controlled clinical trials of antidepressants that involved nearly 4,400 children and adolescents. The review revealed that 4% of those taking antidepressants thought about or attempted suicide (although no suicides occurred), compared to 2% of those receiving placebos.
This information prompted the FDA, in 2005, to adopt a "black box" warning label on all antidepressant medications to alert the public about the potential increased risk of suicidal thinking or attempts in children and adolescents taking antidepressants. In 2007, the FDA proposed that makers of all antidepressant medications extend the warning to include young adults up through age 24. A "black box" warning is the most serious type of warning on prescription drug labelling.
The warning emphasizes that patients of all ages taking antidepressants should be closely monitored, especially during the initial weeks of treatment. Possible side effects to look for are worsening depression, suicidal thinking or behaviour, or any unusual changes in behaviour such as sleeplessness, agitation, or withdrawal from normal social situations. The warning adds that families and caregivers should also be told of the need for close monitoring and report any changes to the physician.
Serotonin Syndrome
Finally, the FDA has warned that combining the newer SSRI antidepressants with one of the commonly-used "triptan" medications used to treat migraine headaches could cause a life-threatening illness called "serotonin syndrome." A person with serotonin syndrome may be agitated, have hallucinations (see or hear things that are not real), have a high temperature, or have unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs (monoamine oxidase inhibitor), but it can happen with the newer antidepressants as well, if they are mixed with the wrong medications.
Other Considerations
SSRIs are better tolerated and are safer in overdose than other classes of antidepressants and therefore are considered first-line drug therapy for treating depression. Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued because of side-effects; toxicity in overdosage is also a problem.
Clinical Trials
The selective serotonin reuptake inhibitors (SSRIs) are the most studied medications for PTSD, with the largest number of double-blind, placebo-controlled trials. Of the SSRIs, sertraline, paroxetine and fluoxetine have been the most extensively studied. These studies have demonstrated that SSRIs are effective in short-term trials (6-12 weeks). Furthermore, continuation and maintenance treatment for 6-12 months decrease relapse rates. Besides being the most studied and effective drugs for PTSD, SSRIs have a favourable adverse effect profile, making them the first-line treatment for PTSD. If SSRIs are not tolerated or are ineffective, non-SSRIs should be considered.
In 2004, two drugs were approved for treating PTSD by the U.S. Food and Drug Administration (FDA). Both were SSRI’s; Paroxetine and Sertraline. FDA approval is based on multi-center double-blind studies.
Studies with fluoxetine and paroxetine have shown that these medications are both superior to placebo among combat veterans. Many studies with civilians and some studies with combat veterans have provided clear evidence that SSRIs, tricyclic antidepressants, and MOI's are useful in treating chronic PTSD. Rates of clinical remission for patients given fluoxetine and paroxetine are around 40% after 3 months, compared with 4% to 18% for those given placebo.
SSRIs have a broad effect on all symptom clusters as well as on all the individual symptoms of PTSD. SSRIs appear to start to work rapidly in patients with chronic PTSD, with improvements in irritability and anger evident as early as during the first week. In this domain, SSRI therapy has a marked, early, and sustained effect.
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