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The active management of depression - Clinical Update

Journal of Family Practice, Sept, 2002 by Larry Culpepper

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Long-term side effects of concern include weight gain and sexual dysfunction. While other SSRIs have low rates for weight gain, paroxetine causes a weight gain of more than 7% (about 10 lbs for a patient of average weight) in 20% to 25% of patients. (39) Some element of sexual dysfunction, most often delayed orgasm, is estimated to occur in 30% to 40% of individuals receiving SSRIs. (40,41) Management options include delaying dosage of agents with a half-life of about 24 hours (escitalopram, citalopram, sertraline). (42) For instance, an individual who usually takes one of these agents in the morning may delay a day's dose until after engaging in sexual intercourse in the evening. While open-label studies support augmentation, particularly with bupropion or buspirone, the few small randomized double-blind trials available suggest that positive results should be interpreted with caution. (43) Alternatively, patients may benefit from sildenafil (44) or a switch to a non-SSRI antidepressant.

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While management of side effects presents one option, the best clinical approach may be to select an agent with minimal side-effect potential. In double-blind randomized trials, escitalopram, a new SSRI treatment option, was demonstrated to require treatment termination in less than 5% of recipients at its usual dose of 10 mg, a rate no different from that of placebo. (45) In contrast, rates of 15% to 30% have been reported for other SSRIs and newer antidepressants at the time of their initial release.

Adjusting Treatment

One recent primary care trial examined the effectiveness of 3 SSRIs: fluoxetine, sertraline, and paroxetine. At the time this study was designed, citalopram was not in common use. While about 75% of patients attained remission, only 40% to 50% of patients were maintained on the first prescribed agent. (24) Additionally, about 20% of depression "treatment resistance" resulted because patients did not fill their prescriptions or adhere to treatment. (46) For patients who do not respond within the first month, increasing the dosage is appropriate. (47) About 25% of patients respond to this adjustment. (48) For patients who do not respond, reassessment of the diagnosis, as well as assessment of potential psychiatric comorbidities and suicidal ideation, is indicated. For nonresponders, and for those with intolerable side effects, switching to a second SSRI is a reasonable next step. (49) About 50% of patients switched to a second agent respond. (50) For those who do not respond, the primary care physician might consider a second medication switch or psychiatric consultation.

Further treatment adjustment is indicated for patients who experience partial response. This might take the form of augmentation with psychotherapy (51) or with another agent. (52) Lithium and thyroid hormone (often as 25 to 50 [micro]g T3 daily) are the most frequently used options, although stimulants, other antidepressants, and atypical antipsychotics are all of value in some patients. (48,49,50)

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The active management of depression - Clinical Update

Journal of Family Practice, Sept, 2002 by Larry Culpepper

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