Approach to the Patient:

· Be very clear and specific about the side effects patients might get.

· Choose an antidepressant that fits best with the patient's medical conditions and side effect preferences.

· When side effects occur, tell the patient if tolerance is likely to develop (see below).

· Consider dosing strategies that can manage certain side effects (see below).

· Then consider switching to a different antidepressant if intolerance is severe, persistent, or if an adequate trial does not produce a remission.

Sexual Problems on SSRIs and venlafaxine: loss of desire, impaired arousal or lubrication, delayed or impaired ejaculation or orgasm. Occurs in about 50% of patients. · All SSRIs do it. Paroxetine has the highest rate, about 10-15% higher than the others according to a meta-analysis. There is considerable individual variation: a patient may have the problem on one SSRI and not on another. · Waiting for up to three months can be helpful in about 50% of patients. But, many patients will not want to wait. · Lowering the dose sometimes helps, but depression will recur in some patients. · Drug holidays (i.e. - skip Friday dose and resume Sunday at Noon) may help 50% of patients, but may reduce efficacy or lead to serotonin withdrawal symptoms, such as dizziness, depressed mood, nausea, and confusion. The discontinuation syndrome is most common with paroxetine due to its short half-life, least common with fluoxetine due to the very long half-life of its active metabolite. · Addition of other drugs (antidepressants, Viagra, etc.) complicates treatment, introduces new side effects, is only variably effective, and is generally not advised.

Recommendations about sexual side effects: In acute phase, if patient is improving, assess quality of life impact of this side effect. If patient is likely to become non-compliant, it probably would be better to switch to a different antidepressant. Otherwise consider dose reduction, waiting, or drug holiday. If a switch is made, first line options would be bupropion SR or nefazodone, or mirtazapine if weight gain is not an important consideration. Second choice would be to try a different SSRI. Another option would be a tricyclic such as nortriptyline, if not high overdose or seizure risk.

Tiredness or sedation on SSRIs · Many patients on SSRIs feel tired during the day. Nevertheless, they may still have disturbed sleep, and they may often need a hypnotic. · Patients usually do not develop tolerance to this side effect. · Most common with paroxetine, although seen with the others. · Addition of an activating drug (caffeine or other stimulants) can be helpful but effects may be brief or variable and they can complicate treatment by introducing new side effects. Recommendations: Try adjusting time of day dose is given. If tiredness remains severe, consider switching to less sedating antidepressant such as bupropion.

Stimulation or restlessness · May be activation of underlying panic-type anxiety disorder. If so, start with a lower dose and see if patient can become adjusted to the medication. · Seems most common with bupropion. Among the SSRIs, fluoxetine (Prozac - non-formulary) does it the most, while the others do it in 10-20% of patients. Citalopram (Celexa) may have the least problem in this area. · Insomnia may be the only important manifestation of stimulation and may be managed with trazodone (causes occasional arrhythmias but is safe for the overwhelming majority of patients according to the conclusions of the APA Practice Guideline for Major Depression, Revised - 2000) or lorazepam. · Tolerance does not usually develop. Recommendations: If activation remains very troubling to the patient, try switching to a different SSRI antidepressant. Consider nefazodone, mirtazapine, or a less activating tricyclic such as nortriptyline, if not high overdose or seizure risk.

Weight gain on SSRIs · Among the SSRIs, paroxetine causes weight gain, while the effect of the others is unclear. Studies are conflicting, but expert opinion suggests they all can cause weight gain over the long term. · Although some patients experience slight weight loss during the first few months on some SSRIs, this does not persist over the long term, and there is no role for SSRIs in the treatment of obesity. However, reports indicate switching to bupropion may be useful for weight loss, especially for patients who gained weight on other antidepressants. Recommendations: If the patient reports distress about the weight gain, consider switching to another antidepressant: bupropion, nefazodone, or other SSRIs. Tricyclics usually cause weight gain so they should be avoided.

Gastrointestinal side effects: nausea, and more rarely diarrhea or vomiting · More common with SSRIs and venlafaxine (Effexor). Less common with bupropion (gives constipation) and tricyclics. · May lead to early termination of trial, but tolerance often develops in a few weeks · Do not use cisapride (Propulsid). H2 blockers may sometimes be helpful. Recommendations: Try lowering dose, taking with meals. If these fail, consider switching medication

Headache · All may cause it, but also these drugs may treat certain headache problems · Tolerance sometimes develops Recommendations: Try NSAIDs short-term, but you may need to switch to a different antidepressant