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The active management of depression - Clinical Update

Journal of Family Practice, Sept, 2002 by Larry Culpepper

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Cognitive behavioral therapy and other psychotherapies can show effectiveness equal to that of pharmacotherapy, although response usually lags by a month to 6 weeks compared with that attained by pharmacotherapy. (32) For moderately to severely depressed patients, pharmacotherapy is the treatment of choice in part because of its more rapid onset of action. (25)

Pharmacotherapy

Pharmacotherapy, most often in the form of an SSRI, is the treatment of choice for depression as a result of patient preference, insurance coverage limitations, or time constraints. In choosing an antidepressant, the family physician should be guided by effectiveness and potential for drug--drug interactions and for both short-and long-term side effects. (33)

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Tricyclics, the SSRIs, and other newer antidepressants offer similar efficacy. (34) While efficacy assesses outcome under ideal treatment conditions, the primary care physician is more concerned with effectiveness, defined as the proportion of patients started on an antidepressant during routine clinical practice who attain lasting benefit. Effectiveness includes consideration of patients who discontinue treatment because of side effects or drug--drug interactions, as well as those who do not obtain adequate therapeutic response. Since about 25% of patients discontinue SSRIs because of side effects, this is an important concern. (24) Few studies have been conducted comparing the effectiveness of antidepressants.

Drug--drug interactions are mediated predominately by the cytochrome P450 isoenzymes responsible for drug metabolism in the liver. (35-37) The 2D6 isoenzyme is responsible for 50% of drug metabolism in the liver; the 3A4 isoenzyme is responsible for another 30%. (38) As a clinical example of the importance of such inhibition, codeine requires 2D6-mediated metabolism to become morphine and is ineffective for pain in many patients who are prescribed a 2D6 inhibitor. Patients receiving such agents also can have a 300% to 400% increase in blood levels of previously stable [beta]-blockers. Paroxetine and fluoxetine, the two SSRIs that strongly inhibit the 2D6 isoenzyme, cause clinically significant interactions; fluoxetine is also a moderate inhibitor of the 3A4 isoenzyme. (35) Because of the number of potential drug--drug interactions through these isoenzymes, physicians must check for interactions before prescribing these medications or adding other new medications in patients already receiving these agents. This also is a consideration for patients who might require additional medications acutely, for instance in response to a cardiac or other emergency.

Side effects of concern include gastrointestinal effects, particularly nausea, and central nervous system (CNS) effects, including anxiety and agitation, sleep disturbance, and tremor. When these occur, they often decrease rapidly over the first 1 to 3 weeks. If severe, they can be managed by a temporary dosage decrease. For patients with significant CNS side effects, altering the timing of the daily dose might provide relief from daytime somnolence or agitation or from nighttime insomnia.

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The active management of depression - Clinical Update

Journal of Family Practice, Sept, 2002 by Larry Culpepper

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