Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants considered the current standard of drug treatment. A possible cause of depression is an inadequate amount of serotonin, a chemical used in the brain to transmit signals between neurons. SSRIs are said to work by preventing the reuptake of serotonin (also known as 5-hydroxytryptamine, or 5-HT) by the presynaptic neuron, thus maintaining higher levels of 5-HT in the synapse. Chemists Klaus Schmiegel and Bryan Molloy of Eli Lilly discovered the first SSRI, fluoxetine. This class of drugs includes:
Citalopram (Celexa, Cipramil)
Escitalopram (Lexapro, Cipralex, Seroplex, Lexamil)
Fluoxetine (Prozac, Sarafem, Symbyax)
Fluvoxamine (Luvox)
Paroxetine (Paxil, Aropax)
Sertraline (Zoloft)
Vilazodone (Viibryd)

These antidepressants typically have fewer adverse effects than the tricyclics or the MAOIs, although such effects as drowsiness, dry mouth, nervousness, anxiety, insomnia, decreased appetite, long-term weight gain and decreased ability to function sexually may occur. Some side effects may decrease as a person adjusts to the drug, but other side effects may be persistent.

Work by two researchers has called into question the link between serotonin deficiency and symptoms of depression, noting that the efficacy of SSRIs as treatment does not in itself prove the link. Research indicates that these drugs may interact with transcription factors known as “clock genes”, which may play a role in the addictive properties of drugs (drug abuse), and possibly in obesity.

A systematic review of randomized controlled trials published in the Archives of General Psychiatry showed that up to one-third of the 6-week effect of SSRI Treatment can be seen in the first week. The same study also found that patients treated with SSRIs were 64% more likely to achieve a 50% absolute reduction in HRSD than patients given a placebo.[1]

Citalopram (Celexa): usual dosing is 20 mg initially; maintenance 40 mg per day; maximum dose 60 mg per day.
Escitalopram (Lexapro, Cipralex): usual dosing is 10 mg and shown to be as effective as 20 mg in most cases. Maximum dose 20 mg. Also helps with anxiety.
Paroxetine (Paxil, Seroxat): Also used to treat panic disorder, OCD, social anxiety disorder, generalized anxiety disorder and PTSD. Usual dose 25 mg per day; may be increased to 40 mg per day. Available in controlled release 12.5 to 37.5 mg per day; controlled release dose maximum 50 mg per day. Less cycling in patients who are bipolar.
Fluoxetine (Prozac): Also used to treat OCD, bulimia, and panic disorder. Long half-life; less withdrawal when medication is stopped. Dosing is 20 mg to a maximum of 80 mg.
Fluvoxamine (Luvox): Although primarily used in the treatment of OCD, a doctor may prescribe it for depression. Initial dose is 50 mg, increasing by 50 mg every 4-7 days. If daily dose is greater than 100 mg give in equally divided doses or give larger dose at bedtime not to exceed 300 mg per day.
Sertraline (Zoloft, Lustral): Also used to treat panic disorder, OCD, PTSD, social anxiety disorder, premenstrual dysphoric disorder. Dosing is 50-200 mg per day and should be titrated upward.

Be aware of drug interactions. Dextromethorphan (found in many brands of over-the-counter cough syrup) as well as the opioids tramadol (Tramal, Ultram), and pethidine/meperidine are contraindicated with all SSRIs as they are serotonin reuptake inhibitors (SRIs) themselves and the combination could cause the potentially fatal serotonin syndrome. Many SSRIs inhibit the metabolism of dextromethorphan as well, further adding to the risk.

Drug interactions may also occur when concurrently taking phenytoin (Dilantin) and warfarin (Coumadin) (phenytoin and warfarin levels are increased).

Always check with pharmacy regarding potential drug interactions.[2]

Source:

[1]http://en.wikipedia.org/wiki/Antidepressant

[2]http://en.wikipedia.org/wiki/List_of_antidepressants

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When was the SSRI discontinuation syndrome first recognized?

Reports began to emerge soon after the SSRIs were introduced in the late 1980s.

How common is it? The incidence and prevalence of this syndrome is not yet known. The few available discontinuation studies indicate minor forms of the syndrome may be common and severe forms unusual. A retrospective chart review of 171 clinic patients who discontinued an SSRI while under supervision, reported at least one new symptom in 20% and 14% of patients stopping paroxetine (Paxil) and fluvoxamine (Luvox), respectively. Abrupt discontinuation of fluvoxamine was associated with new symptoms in 12 of 14 subjects (86%) in a prospective, open-label panic study. In a randomized placebo-controlled trial of paroxetine for panic, 19/55 (34%) experienced withdrawal symptoms. Abrupt discontinuation of fluoxetine (Prozac) in a randomized placebo controlled study of 299 subjects did not appear to cause many symptoms. No published study of sertraline (Zoloft) discontinuation symptoms is yet available but there are several case reports.

What are the signs and symptoms of the SSRI discontinuation syndrome?

Neurologic symptoms (dizziness, vertigo, lightheadedness and gait instability) are most commonly reported, followed by somatic complaints (nausea, emesis, fatigue and headache) and not uncommonly, insomnia. Still characteristic but reported less frequently are shock-like sensations, parasthesia, visual disturbances, diarrhea, myalgias and chills. A range of nonspecific mental symptoms including agitation, impaired concentration, vivid dreams, depersonalization, irritability and suicidal thoughts have been reported. When allowed to run its course, the syndrome duration is variable (one to several weeks) and ranges from mild-moderate intensity in most patients, to extremely distressing in a small number.

What other factors should clinicians consider when identifing this syndrome?

The duration of SSRI use is usually 1 month with symptoms developing 2-5 days after SSRI discontinuation or dose reduction. When symptoms emerge in this context, clinicians should be encouraged to include the discontinuation syndrome on their list of differential diagnoses. Awareness of some of the more unusual symptoms, such as dizziness and shock-like sensations, and re-education of patients prior to stopping or tapering an SSRI, should prevent unnecessary and expensive medical investigations.

What is the mechanism behind this problem?

The biological mechanisms underlying this syndrome are not well understood, although an acute decrease in synaptic serotonin in the face of down-regulated or desensitized serotonin receptors has been postulated.

Who is at risk?

The SSRI discontinuation syndrome does not appear to discriminate based on age, sex, diagnosis or dose of SSRI (both low and high doses have been reported). As I mentioned, there appears to be less risk with the abrupt interruption of fluoxetine. Paroxetine is the SSRI most often mentioned in the case reports and the reason for this may be as simple as the fact that it is most frequently prescribed. An alternative explanation may involve paroxetine s affinity for cholinergic (muscarinic) receptors, causing cholinergic rebound on discontinuation. However, this explanation wouldn’ t account for the full spectrum of symptoms described.

Can it be avoided or treated?

Review of the SSRI discontinuation literature suggests that symptoms may occur even if the SSRI dose is tapered gradually. In half of 50 reported cases, an attempt was made to taper the SSRI, although details concerning the duration and rapidity of taper were not provided consistently. At this point, it is unclear whether tapering SSRIs will reduce the risk nor is it clear whether we should advocate the routine taper of SSRIs when stopping treatment. The only known effective treatment is the re-introduction of the SSRI which is associated with rapid resolution of symptoms. Unfortunately, the syndrome tends to recur in approximately 75% of patients when the same SSRI is later discontinued.

Source: http://www.circlemedhealthcare.com/ssri.pdf

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Lustral tablets contain the active ingredient sertraline hydrochloride, which is a type of antidepressant known as a selective serotonin reuptake inhibitor (SSRI). (NB. Sertraline tablets are also available without a brand name, ie as the generic medicine.)

Antidepressant medicines act on nerve cells in the brain. In the brain there are numerous different chemical compounds called neurotransmitters. These act as chemical messengers between the nerve cells. Serotonin is one such neurotransmitter and has various functions that we know of.

When serotonin is released from nerve cells in the brain it acts to lighten mood. When it is reabsorbed into the nerve cells, it no longer has an effect on mood. It is thought that when depression occurs, there may be a decreased amount of serotonin released from nerve cells in the brain.

SSRIs work by preventing serotonin from being reabsorbed back into the nerve cells in the brain. This helps prolong the mood lightening effect of any released serotonin. In this way, sertraline helps relieve depression.

Sertraline may also be used in the treatment of obsessive compulsive disorder and post-traumatic stress disorder. It is not fully understood how it works in these conditions.

It may take between two to four weeks for the benefits of this medicine to appear, so it is very important that you keep taking it, even if it doesn’t seem to make much difference at first. If you feel your depression has got worse, or if you have any distressing thoughts or feelings in these first few weeks, then you should talk to your doctor.
What is it used for?
Depression in adults
A psychiatric disorder in which tasks are excessively repeated (obsessive-compulsive disorder) in adults and children aged six years and over
Post-traumatic stress disorder in adult women
Warning!
Depression and other pschiatric illnesses are associated with an increased risk of suicidal thoughts, self-harm, and suicide. You should be aware that this medicine may not start to make you feel better for at least two to four weeks. However, it is important that you keep taking it in order for it to work properly and for you to feel better. If you feel your depression or anxiety has got worse, or if you have any distressing thoughts, or feelings about suicide or harming yourself in these first few weeks, or indeed at any point during treatment or after stopping treatment, then it is very important to talk to your doctor.
This medicine may reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won’t affect your performance.
It is recommended that you avoid drinking alcohol while taking this medicine.
SSRI antidepressants have been associated with the development of unpleasant or distressing restlessness and the need to move, often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. If you experience these symptoms you should consult your doctor.
Antidepressants may cause the amount of sodium in the blood to drop – a condition called hyponatraemia. This can cause symptoms such as drowsiness, confusion, muscle twitching or convulsions. Elderly people may be particularly susceptible to this effect. You should consult your doctor if you develop any of these symptoms while taking this medicine, so that your blood sodium level can be checked if necessary.
If you experience seizures (convulsions or fits) while taking this medicine, consult your doctor immediately, as you will need to stop treatment with this medicine. This also applies if you suffer from epilepsy and experience more seizures than normal after starting this medicine.
You should not suddenly stop taking this medicine, as this can cause withdrawal symptoms such as dizziness, sleep disturbances (including intense dreams), nausea, headache, a feeling of weakness, pins and needles and anxiety. Withdrawal symptoms are temporary and are not due to addiction or dependence on the medicine. They can usually be avoided by stopping the medicine gradually, usually over a period of weeks or months, depending on your individual situation. Follow the instructions given by your doctor when it is time to stop treatment with this medicine. On very rare occasions some people have experienced withdrawal symptoms after accidentally missing a dose of this medicine.
Following a review of the safety and efficacy of SSRIs to treat depression in children under 18 years of age (unlicensed use), the Committee on Safety of Medicines (CSM) has concluded that the risks of sertraline outweigh the benefits for treating depressive illness in this age group. If you are under 18 and taking sertraline for depression you should consult your doctor for advice, but do not suddenly stop taking it as this can cause withdrawal symptoms. Sertraline may be used for obsessive-compulsive disorder in children aged six years and over, but is not recommended for younger children.
Use with caution in
Elderly people
Young adults
History of suicidal behaviour or thoughts
History of mania or hypomania
People also receiving electroconvulsive therapy (ECT)
Decreased kidney function
Decreased liver function
Diabetes
Epilepsy
History of bleeding disorders
People taking medicine that affects blood clotting (eg anticoagulants such as warfarin)
Not to be used in
Children and adolescents under 18 years of age for the treatment of depressive illness
People who have taken a monoamine-oxidase inhibitor antidepressant (MAOI) in the last 14 days
Manic episodes of manic depression (bipolar affective disorder)
Severely decreased liver function
Uncontrolled epilepsy
People taking the antipsychotic medicine pimozide

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.
Pregnancy and Breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.
The safety of this medicine in pregnancy has not been established. It should therefore be used with caution during pregnancy, and only if the benefits to the mother outweigh any risks to the foetus. Seek medical advice from your doctor.
This medicine passes into breast milk, however the effect of this on the nursing infant is unknown. For this reason women who need to take this medicine should consider not breastfeeding. Seek medical advice from your doctor.
Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.
Disturbances of the gut such as nausea, vomiting, diarrhoea or abdominal pain
Indigestion (dyspepsia)
Loss of appetite
Shaking, usually of the hands (tremor)
Dizziness
Difficulty in sleeping (insomnia)
Sleepiness (somnolence)
Increased sweating
Dry mouth
Sexual problems
Headache
Anxiety and agitation
Pins and needles (paraesthesia)
Changes in blood pressure
Seizures
Loss of memory (amnesia)
Liver disorders

The side effects listed above may not include all of the side effects reported by the drug’s manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.
How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

Sertraline should not be taken at the same time as monoamine oxidase inhibitor medicines (MAOIs). These include monoamine oxidase inhibitor antidepressants such as phenelzine, tranylcypromine and moclobemide, the antibiotic linezolid and the anti-Parkinson’s medicine selegiline. Sertraline should not be started until at least at least a day after stopping moclobemide or linezolid, and at least two weeks after stopping other monoamine oxidase inhibitors. Similarly, treatment with any MAOIs should not be started until at least two weeks after stopping treatment with sertraline.

Sertraline must not be taken with the antipsychotic medicine pimozide.

Sertraline should not be taken in combination with benzodiazepines or other tranquilisers by people who need to drive or operate machinary.

There may be an increased risk of side effects if sertraline is taken with the following medicines, which also enhance the activity of serotonin in the brain:
lithium
triptans for migraine, eg sumatriptan
tramadol
tryptophan.

The herbal remedy St John’s wort should not be taken with sertraline for the same reason.

Sertraline may increase the blood levels of the following medicines:
clozapine
some tricyclic antidepressants (imipramine, desipramine, nortriptyline and possibly amitriptyline).

Sertraline may increase the effect of anti-blood-clotting medicines (anticoagulants) such as warfarin, and this may increase the risk of bleeding. If you are taking an anticoagulant with this medicine, your blood clotting time should be regularly monitored.

As SSRIs have been associated with bleeding abnormalities, the following medicines, which are known to affect the ability of the blood to clot, should be used with caution with sertraline:
tricyclic antidepressants
some antipsychotic medicines
some antisickness medicines, eg prochlorperazine
aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen
ticlopidine
dipyridamole.

Treatment with this medicine may alter control of blood sugar in people with diabetes, who may need an adjustment in their dose of insulin or antidiabetic tablets. People with diabetes should discuss this with their doctor.

Sertraline blood levels may be increased by cimetidine and this may increase the risk of sertraline side effects.
Other medicines containing the same active ingredient

Sertraline tablets are available without a brand name, ie as the generic medicine.

Source: http://www.netdoctor.co.uk/medicines/100001555.html

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Zoloft is well tolerated and effective for the treatment of depression and certain anxiety conditions.

Zoloft is FDA approved to treat depression, certain types of social anxiety conditions, posttraumatic stress disorder (PTSD), panic disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD) in adults over age 18. It is also approved for OCD in children and adolescents age 6-17 years.

For more than 15 years, Zoloft has safely and effectively treated millions of people with depression and certain anxiety conditions. Zoloft is available in multiple strengths, so your doctor can decide a dose for you.

Zoloft® (sertraline HCl) is a type of antidepressant known as a selective serotonin reuptake inhibitor (SSRI). It’s approved to treat depression, social anxiety disorder, posttraumatic stress disorder (PTSD), panic disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD) in adults over age 18. It is also approved for OCD in children and adolescents age 6-17 years.

Important Safety Information

Depression is a serious medical condition, which can lead to suicidal thoughts and behavior. Children, adolescents, and young adults taking antidepressants may be at increased risk for suicidal thoughts and behavior within the first few months of treatment. This risk must be balanced with the medical need. Those starting medication or changing doses should be watched closely for suicidal thoughts, worsening of depression, or unusual changes in mood or behavior. In children and teens, Zoloft is only approved for use in those with obsessive-compulsive disorder. A patient Medication Guide about “Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available.
Zoloft is not for everyone. People taking MAOIs or pimozide shouldn’t take Zoloft. Concomitant use of Zoloft with NSAIDs or aspirin may be associated with an increased risk of bleeding. Side effects may include dry mouth, insomnia, sexual side effects, diarrhea, nausea and sleepiness. In studies, few people were bothered enough by side effects to stop taking Zoloft. Side effects may result from stopping Zoloft particularly when abrupt. You should, however, stop taking Zoloft if you get any of the following symptoms of Serotonin Syndrome, a rare but life-threatening reaction, such as fever, sweating, muscle stiffness, trouble thinking clearly, a change in mental functioning, sleepiness, or change in your breathing, heartbeat and blood pressure.
You should tell your doctor if you are pregnant or plan to become pregnant, as there is a potential risk to the fetus with Zoloft. Like many antidepressants, Zoloft can be present in breast milk so tell your doctor if you are nursing.
Zoloft is approved to treat depression, social anxiety disorder, posttraumatic stress disorder (PTSD), panic disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD) in adults over age 18. It is also approved for OCD in children and adolescents age 6-17 years.
Zoloft is not habit-forming and is not associated with weight gain. So talk to your doctor about how Zoloft might help you. Zoloft comes in 25-mg, 50-mg, and 100-mg tablets. You and your doctor can discuss a dose for you.
Source: http://www.zoloft.com

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By LAURA BLUE/LONDON Tuesday, Feb. 26, 2008
Source: http://www.time.com/time/health/article/0,8599,1717306,00.html?iid=sphere-inline-bottom

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Overview
Paxil is the brand name for Paroxetine, a phenylpiperidine derivative. Paxil is an SSRI – Selective Serotonin Reuptake Inhibitor, which is a type of antidepressant. SSRIs work by increasing levels of serotonin (a neurotransmitter) to normal.

Paxil’s effects can usually be felt within one to four weeks.

Why is this drug prescribed?
Paxil is used primarily to treat Obsessive-Compulsive Disorder (OCD.)

Paxil is also used to treat:
depression
panic disorder / panic attacks
diabetic nerve pain (neuropathy)
chronic tension headaches
social anxiety disorder (social phobia)
premature ejaculation
premenstrual syndrome (PMS)

Warnings
The safety and effectiveness of Paxil in children under 18 years old have not been established.

Paxil is not addictive. Suddenly discontinuing Paxil may lead to withdrawal symptoms such as confusion, dizziness, sweating, or tremors. Dosage should be gradually tapered when Paxil is discontinued.

Paxil does not usually cause sedation, but patients should not drive or operate heavy machinery until it is known that Paxil does not affect the ability to safely engage in these activities.

For Pregnant or Nursing Mothers: One study showed no adverse effects due to Paxil during pregnancy, but further study is required and pregnant women are not advised to take Paxil. Paxil passes into human breast milk, and nursing mothers should not take Paxil.

Contraindications
Paxil should Not be used for people with an allergy or hypersensitivity to this drug or any SSRI.

Precautions
Paxil may be used with caution in people with the following conditions:
liver or kidney disease – lower dosage may be needed
seizures (epilepsy or convulsions) – risk of seizures is increased
a history of mania – Paxil may activate mania
elderly – lower dosage may be needed
brain disease or damage
mental retardation

Adverse Reactions
Paxil may cause the following reactions:
lowered blood pressure and fainting upon standing (postural hypotension)
sweating
dry mouth
nausea
headache
drowsiness
sedation
nervousness
insomnia
constipation
weakness
loss of appetite
taste disorders
tingling in hands
upset stomach
dizziness
blurred vision
itching
chills
abnormal ejaculation
impotence
sexual dysfunction
diarrhea
hypomania
seizures

Interactions with Drugs and Other Substances
Drugs or substances that may interact with Paxil are:
MAO Inhibitors (within 14 days) – serious or even fatal interactions can occur when taken with Paxil
benzodiazepines, desipramine, Haldol (haloperidol), and Normodyne (labetalol) – Paxil may increase the effects of these drugs
Dilantin (phenytoin) – can decrease blood levels of Paxil and reduce its effects
Quinaglute (quinidine) and Tagamet(cimetidine) – can increase Paxil levels and lead to drug toxicity
Astemizole (Hismanal) – can lead to a serious change in heart rhythm when taken with Paxil
Ultram (tramadol) – can increase the risk of seizures when taken with Paxil
Tryptophan – can increase side effects such as sweating, nausea, and dizziness when taken with Paxil
Coumadin (warfarin) – can cause bleeding when taken with Paxil
Moclobemide (Manerex) within 3 to 7 days
Buspirone (BuSpar), Bromocriptine (Parlodel), Dextromethorphan (cough medicine), Levodopa (Sinemet), Lithium, Meperidine (Demerol), Nefazodone (Serzone), Pentazocine (Talwin), other SSRIs (such as: Citalopram [Celexa], fluoxetine [Prozac], fluvoxamine [Luvox], sertraline [Zoloft]), LSD, MDMA (ecstasy), marijuana, Sumatriptan (Imitrex), Tramadol (Ultram), Trazodone (Desyrel), Tryptophan, Venlafaxine (Effexor) – taking these medicines with Paxil can increase the chance of developing a rare, but very serious, unwanted effect known as the serotonin syndrome, whose symptoms include confusion, diarrhea, fever, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, or twitching.

Source: http://whatmeds.stanford.edu/medications/paroxetine.html

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