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which blocks the reuptake of serotonin but also inhibits the 5HT2 postsynaptic receptors; and mirtazapine, which selectively blocks presynaptic 2-adrenergic receptors and enhances both noradrenergic and serotonergic transmission All of these antidepressants are effective in the treatment of depression, both typical and atypical The SSRI drugs have been effective in the treatment of panic attacks, bulimia, generalized anxiety disorder, OCD, and PTSD They do not seem to be as clearly effective in some pain syndromes as the TCAs, although venlafaxine may have some efficacy in the treatment of neuropathic pain, and duloxetine is FDAapproved for the treatment of diabetic peripheral neuropathy Most of the drugs in this group tend to be activating and are given in the morning so as not to interfere with sleep Some patients, however, may have sedation, requiring that the drug be given at bedtime This reaction occurs most commonly with paroxetine, fluvoxamine, and mirtazapine The SSRIs can be given in once-daily dosage Nefazodone and venlafaxine are usually given twice daily Bupropion and venlafaxine are available in extendedrelease formulations and can be given once daily There is usually some delay in response; fluoxetine, for example, requires 2 6 weeks to act in depression, 4 8 weeks to be effective in panic disorder, and 6 12 weeks in treatment of OCD The starting dose (10 20 mg) is the usual daily dose for depression, while OCD may require up to 80 mg daily Some patients, particularly the elderly, may tolerate and benefit from as little as 10 mg/d or every other day The other SSRIs have shorter half-lives and a lesser effect on hepatic enzymes, which reduces their impact on the metabolism of other drugs (thus not increasing significantly the serum concentrations of other drugs as much as fluoxetine) The shorter half-lives also allow for more rapid clearing if adverse side effects appear Venlafaxine appears to be more effective with doses greater than 200 mg/d, although some individuals respond to doses as low as 75 mg/d The side effects common to all of these drugs are headache, nausea, tinnitus, insomnia, and nervousness Akathisia has been common with the SSRIs; other extrapyramidal symptoms (eg, dystonias) have occurred infrequently but particularly in withdrawal states Sexual side effects of erectile dysfunction, retrograde ejaculation, and dysorgasmia are very common with the SSRIs Antidotes to SSRI-induced sexual dysfunction are occasionally helpful Sildenafil, 25 50 mg 1 hour prior to sexual activity, can improve erectile dysfunction in some patients Cyproheptadine, 4 mg orally prior to sexual activity, may be helpful in countering drug-induced anorgasmia Adjunctive bupropion (75 150 mg daily) may also help with restoring erectile function The SSRIs are strong serotonin uptake blockers and may in high dosage or in combination with MAO inhibitors, including the antiparkinsonian drug selegiline, cause a serotonin syndrome This syndrome is manifested by rigidity, hyperthermia, autonomic instability, myoclonus, confusion, delirium, and coma This syndrome can be a particularly troublesome problem in the elderly Several cases of angina have been reported in association with SSRIs However, current research indicates that SSRIs are safer agents to use than TCAs in patients with cardiac disease A study has found that sertraline is a safe and.

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