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Overview 



Selective serotonin reuptake inhibitors (SSRIs) are medications widely prescribed for the treatment of depression, obsessive-compulsive disorder, bulimia, anorexia nervosa, panic disorder, and social phobia. The majority of all antidepressants prescribed in the United States are from the SSRI family. Commonly prescribed SSRIs include fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine. SSRI toxicity and other adverse drug reactions can occur with overdose, in combination with other medications, or infrequently at therapeutic doses.



Therapeutic Usage


SSRIs work by blocking a receptor in the brain that absorbs the chemical serotonin. Serotonin is one of several chemicals called neurotransmitters; each nerve cell generally uses one of these chemicals to pass on messages on other nerve cells. When not enough serotonin is released by the first nerve cell, the message won't get through the next nerve cell: this is one of the changes that appears to be important in causing depression.

Nerve cells normally recycle serotonin by reabsorbing it, and the SSRIs work by inhibiting this re-uptake of serotonin. As a result, more serotonin will be present to pass on messages to nerve cells nearby. SSRIs work selectively on serotonin and have the power to mildly influence mood, outlook, and behavior. Although often positive, these benefits can also be a cause of concern to many people.

Harmful Side Effects


The side effects that the SSRIs tend to cause most commonly include:

  • nausea
  • diarrhoea
  • constipation
  • loss of appetite (sometimes increased appetite and weight gain)
  • dry mouth
  • headache
  • insomnia (sometimes drowsiness)
  • tremor (shakiness)
  • sweating
  • light-headedness
  • problems with sexual arousal and delayed orgasm.

SSRIs can worsen anxiety at the start of treatment even though they are prescribed to treat anxiety, but this usually only lasts for a brief period.

Toxicity


SSRIs have a high therapeutic to toxicity ratio and are associated with less toxicity than other antidepressants. However, SSRIs taken together with other proserotonergic agents can precipitate the potentially lethal "serotonin syndrome" (SS), a drug reaction that causes the body to have too much serotonin. These proserotonergic agents include monoamine oxidase inhibitors (MAOIs), lithium, opioids, and amphetamine/stimulants, including 3,4 methylenedioxymethamphetamine (MDMA, Ecstasy), cocaine, and herbal dietary supplements or nutraceuticals (St. John's wort, ginseng, and S-adenosyl-methionine). Less frequently, SS can be precipitated by overdose of a single SSRI.

Symptoms of serotonin syndrome (SS) occur within minutes to hours, and may include:

  • Agitation or restlessness
  • Diarrhea
  • Fast heart beat
  • Hallucinations
  • Increased body temperature
  • Loss of coordination
  • Nausea
  • Overactive reflexes
  • Rapid changes in blood pressure
  • Vomiting

Addiction to SSRIs


It is possible for SSRIs to produce unpleasant withdrawal symptoms when they are stopped abruptly. Withdrawal symptoms may include:

  • dizziness
  • numbness and tingling sensations
  • digestive disturbances (particularly nausea and vomiting)
  • headache
  • sweating
  • anxiety
  • sleep disturbances, including vivid dreams.

It seems that paroxetine is more commonly associated with withdrawal symptoms than other SSRIs, and fluoxetine least commonly. Withdrawal symptoms can be minimized or avoided entirely if the dose of the SSRI is gradually decreased over a period of a few weeks.

If withdrawal symptoms do occur, they are temporary and do not include cravings for the medication. SSRIs do not cause addiction in the way cocaine, tobacco, or heroin do. After a period of exposure to SSRIs, however, the brain does adapt and get "used to" the medicine.

SSRIs and Suicide


A lot of publicity has been given to a few reports of people becoming suddenly suicidal while taking fluoxetine or paroxetine.

As a result, all SSRIs have been examined by the Medicines and Healthcare Regulatory Authority (MHRA), the agency of the Department of Health that ensures medicines in the UK meet appropriate standards of safety, quality and effectiveness. After studying all the available research, the MHRA decided in December 2003 that SSRIs (with the exception of fluoxetine) should not be prescribed for children under 18 because they may more do more harm than good in this age group.  In December 2004, the MHRA found that evidence linking SSRIs to suicidal behavior in adults is weak and that the benefits of these medicines in adults generally outweigh any risks. The SSRIs are proven to be very effective treatments for depression and most likely, it is the depressive illness itself that leads to suicidal feelings.

References


1. Selective serotonin re-uptake inhibitors

2. SSRIs: Myths and Facts About Antidepressants

3. Selective Serotonin Reuptake Inhibitor Toxicity

4. Serotonin syndrome

5. Blachford S.L. and Krapp K. eds. Drugs and Controlled Substances Information for Students, Detroit:Thomson Gale, 2003.Drummond, Edward H. The Complete Guide to Psychiatric

6. Olson K.R. ed. Poisoning & Drug Overdose,4th ed. New York: Lange Medical Books, 2004.

7. Drummond, Edward H. The Complete Guide to Psychiatric Drugs: Straight Talk for Best Results. New York: John Wiley &
Sons, Inc., 2000.

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