Selective Serotonin Reuptake Inhibitors (SSRIs)

Starting with Prozac (fluoxetine) about 20 years ago, the SSRIs as a class of mainly antidepressants are widely used today. As their name suggests, the SSRIs affect serotonin in the brain, which explains why they are called “selective”.

There are many different brain circuits in the brain which serotonin affects and each of these regulates a different function: mood, sleep, appetite and sexuality among them.

SSRIs amplify serotonin’s effects by slowing its removal from the synapse between brain cells. With more serotonin to transmit, the neurons help bring serotonin back into balance, and with this balance comes an improvement in mood. SSRIs produce anti-anxiety effects as well – a highly desirable feature in depressed patients who are also anxious. And they are much safer than the tricyclic antidepressants (TCAs) or the monoamine oxidase inhibitors (MAOIs), resulting in very few deaths with overdose.

Because the SSRIs do not affect the cholinergic system, they have none of the anticholinergic effects associated with TCAs. The most common side effects associated with the TCAs are dry mouth, blurred vision, trouble urinating and constipation.TCAs also impair concentration and memory and weight gain is common. Serotonin, in turn, serves as a sort of

  • Drowsiness and lethargy disappear with time, but when first starting the medication, limit alcohol use and avoid sedatives and antihistamines which can worsen the problem. Also avoid driving a car or operating machinery if drowsiness occurs.
  • Report energizing effects including agitation and insomnia to your doctor if they occur. These effects may be reduced by taking fluoxetine, for example, in the morning.
  • Take the medication with food if nausea or heartburn occur.
  • Try reading under a bright light and hold book at a distance or wearing reading glasses if blurred vision occurs. Prescribed eye drops may also help.
  • Get up slowly if you are lying or sitting down to minimize dizziness.
  • Use talcum powder if sweating occurs.
  • Choose analgesics without codeine to treat headaches; some SSRIs inactivate codeine and analgesics without codeine are likely to be more effective in headache management.
  • Report changes in sexual performance or desire to your doctor.
  • Chew sugarless gum or suck on sugarless candy to increase salivation if dry mouth occurs. Frequent tooth brushing helps too.
  • Increase dietary fibre, exercise more often and drink lots of fluids if constipation occurs.
  • If you miss a dose, and are taking medication several times a day, take the missed dose when you remember. If you take all of the medication in the morning and miss a dose by more than 4 to 5 hours, skip the missed dose and continue with the next scheduled dose.
  • Don’t stop your drug suddenly, otherwise you may experience muscle aches, chills, nausea, vomiting or dizziness.

Differences between the SSRIs

As a class of antidepressant agents, the SSRIs share many features, including side effects. However, they do vary in side effect intensity and likelihood of these effects occurring. If one medication within this class of antidepressants proves troublesome, a different medication still within the same drug class may be better tolerated. Here’s a short list of how the SSRIs differ. (From the Clinical Handbook of Psychotropic Drugs. 6th revised edition. Editors Kalyna Z. Bezchlibnyk-Butler, J. Joel Jeffries. Clarke Institute of Psychiatry, Toronto, Canada.)

Anticholinergic effects (dry mouth, blurred vision, constipation, sweating, problems with urination): As a drug class, the SSRIs do not cause significant side effects in this category. Fluoxetine is least likely to cause dry mouth; fluoxetine and sertraline least likely to cause constipation as well as sweating. Blurred vision and problems with urination are uncommon and equally likely with each of the four agents.

Central nervous system (CNS) effects (drowsiness, sedation, insomnia, excitement, confusion, headache): Drowsiness and sedation are equally likely with all four agents, as is insomnia (especially with fluoxetine if given in the evening). Excitement and confusion are least likely with paroxetine, while the incidence of headache is similar with all four agents.

Tremor: All four agents are equally likely to cause tremor.

Dizziness: Fluvoxamine is least likely to cause dizziness.

Stomach upset (nausea): Fluvoxamine and sertraline are most likely to cause stomach upset but upset stomach is common with all SSRIs.

Weakness/fatigue: Sertraline is least likely to cause weakness or fatigue.

Weight gain/loss: All four agents are associated with equal weight loss.

Sexual dysfunction: Sertraline is least likely to cause sexual disturbances.

Other Modern Antidepressants – Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

There are a number of new antidepressants that have properties that are often special to that particular agent. These medications include venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq) and bupropion (Wellbutrin).

Venlafaxine (effexor) affects the reuptake pump by preventing the depletion of a brain chemical, norepinephrine, which is also implicated in depression and anxiety. Stomach upset (mainly nausea) appears to be the most common side effect reported with Effexor use, but headache, somnolence, dry mouth and dizziness have also been noted.

Duloxetine (Cymbalta) is an SNRI, and works by helping restore the balance of serotonic and norepinephrine in the brain and body. Cymbalta helps to block the reuptake of serotonin and norepinephrine so that more remains in the space between the brain’s nerve cells.Dose-depndent nausea, usually lasting about a week, is the most frequently reported adverse drug reaction.

Desvenlafaxine (Pristiq) belongs to the class of antidepressant medications known as selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works on the central nervous system (CNS) to elevate mood by increasing the amount of two neurotransmitters: serotonin and norepinephrine.

Bupropion (Wellbutrin) blocks the removal of another important brain chemical, dopamine, as well as norepinephrine, from the gap between transmitting and receiving neurons, the net effect of which is to alleviate depression. Reported side effects with Wellbutrin include restlessness, agitation, insomnia, tremor, headache and, in excessively high doses (although rarely) seizures. On the plus side for many depressed patients, Wellbutrin does not cause weight gain and about one-quarter of patients who take the medication report weight loss. Wellbutrin is also not associated with loss of sexual desire as are some of the SSRIs, nor is orgasmic or erectile function impaired. Hence, if sexual side effects from other antidepressant medications prove troublesome, it may be possible to switch to a different medication such as Serzone or Wellbutrin to lessen these effects.

How to minimize side effects associated with the newer cyclic antidepressants

  • Use analgesics if headache persists with Effexor.
  • Take Effexor with food if nausea occurs.
  • Chew sugarless gum, or use sugarless candy to increase salivation if dry mouth occurs with any of the medications. Frequent tooth-brushing helps too.
  • Use talcum powder if sweating occurs.
  • Don’t stop Effexor, or Wellbutrin abruptly, otherwise withdrawal symptoms may occur including muscle aches, dizziness, headache, nausea, chills and diarrhea.