Selective Serotonin Reuptake Inhibitors

The selective serotonin reuptake inhibitors (SSRIs) are now commonly used initially in the treatment of major depression. They have a potent and selective blocking effect on the reuptake of serotonin by CNS presynaptic nerve terminals. They have weak, if any, effect on noradrenergic, dopaminergic, histaminergic, and muscarinic cholinergic receptors. Moreover, they do not have a quinidine-like effect on cardiac conduction.

The most frequently used SSRIs are fluoxetine hydrochloride, sertraline hydrochloride, and paroxetine hydrochloride, and I will discuss only these three. Because of their receptor-specific properties, these three SSRIs do not cause orthostatic hypotension, cardiac conduction abnormalities, dry mouth, constipation, or (in general) urinary retention. Sedation is relatively uncommon.

Potential side effects include nausea, anorexia, more frequent or loose stools, anxiety, restlessness, sleep disturbance (insomnia or hypersomnia), headache, diminished sexual drive, orgasmic dysfunction, and apathy. Sinus bradycardia is an uncommon side effect but is rarely symptomatic. Most of these adverse effects are mild or transient, and thus most patients tolerate SSRIs well in the short term. Over the long haul, however, up to 20 percent of patients will discontinue these drugs because of persistent changes in sexual drive or function, and a smaller number will discontinue use because of apathy, gastrointestinal disturbance, or sleep disturbance. Sertra-line hydrochloride is most likely to cause diarrhea, and paroxetine hy-drochloride to cause hypersomnia.

If diminished sexual drive, impotence, or anorgasmia develops during SSRI treatment, lowering the dosage of the drug may resolve the problem. If not, the physician should consider changing to a different class of anti-depressant.

No strong correlation between serum levels of SSRIs and treatment outcome has been demonstrated. Thus, routine monitoring of such levels is not clinically useful.

Fluoxetine hydrochloride has a particularly long half-life: three days or more for the parent drug and a week or more for the active metabolite. For this reason, plateau levels are not rapidly achieved after changes in dosage. Paroxetine hydrochloride and sertraline hydrochloride have half-lives of about a day, similar to the TCAs.

Elderly patients can begin taking fluoxetine hydrochloride at 10 mg po qam, increasing it to 20 mg po qam after a week if the drug is well tolerated. Younger patients can usually take 20 mg po qam from the outset of treatment. Most patients begin to respond to such doses within the first several weeks. An increase to 30 mg po qam in elderly patients or 40 mg po qam in younger patients is indicated if there is no response by six weeks. Few patients require more than 40 mg per day, the average monthly cost of which is $180. If improvement is attained but intolerable side effects develop, a return to a lower dosage often solves the problem without a relapse. The patients clinical state and fluoxetine hydrochlorides long half-life may have led to changes in dosage before plateau levels were reached, so dose reductions because of adverse effects may still keep the patient at an effective antidepressant level.

Sertraline hydrochloride is generally begun at 50 mg po qam and increased to 100 mg po qam after the first week. A subsequent increase to 150 mg po qam is made if there is no improvement by four weeks. The maximum dose is 200 mg per day, which costs approximately $180 per month.

Paroxetine hydrochloride is begun at 10 mg po qhs in elderly patients and 20 mg qhs in others. Dose increases are made to 20 or 30 mg po qhs, respectively, if there is no response in the early weeks of treatment. The maximum dose is 40 mg po qhs in elderly patients and 50 mg po qhs in younger ones. The average monthly cost of 40 mg per day is $95. Some patients find paroxetine hydrochloride sedating and tolerate it best when taken at bedtime.

The SSRIs have a wide range of potential drug interactions because of their effects on the hepatic microsomal enzyme systems. These interactions are often minor, but some can be dangerous. The metabolic inhibition of some commonly prescribed drugs by SSRIs is presented in Table 2.1.

When beginning patients on SSRIs, the physician should specifically dis-

Table 2.1. Metabolic Inhibition of Some Commonly Prescribed Drugs by Selective Serotonin Reuptake Inhibitors (SSRIs)

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Do Not Panic

Do Not Panic

This guide Don't Panic has tips and additional information on what you should do when you are experiencing an anxiety or panic attack. With so much going on in the world today with taking care of your family, working full time, dealing with office politics and other things, you could experience a serious meltdown. All of these things could at one point cause you to stress out and snap.

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