Because they do not bind as avidly as tricyclic drugs to the muscarinic and adrenergic receptors in the brain, they produce fewer side effects, but some patients complain of anxiety or insomnia when they are first introduced. These drugs share the same side effects to varying degrees, including the danger of concomitant MAO inhibitor administration.
The risk of seizures related to the taking of certain of these medications has been much discussed. For the most part, the risk is quite small but there is little information to guide their use in known epileptics. Several studies suggest that the frequency of convulsions may increase in such patients. Bupropion has been particularly associated with seizures in about 0.5 percent of patients treated at higher dose levels (over 400 mg/d) and this drug should not be used in individuals with a history of seizures.
The SSRI drugs are well tolerated, may be effective in a shorter time than the tricyclic agents and are very popular at the moment, but their long-term therapeutic usefulness in comparison with their predecessors remains to be determined (see review of Richelson). Fluoxetine has also been used with benefit in a group of autistic children (see “Course, Treatment, and Prognosis” under “Autism” in Chap. 37). Constipation, dry mouth, and reduced sexual potency are to be expected to some, but varying degrees. Hyponatremia is a rare complication.
The symptoms of a “serotonin syndrome” that results from excessive intake of the above listed drugs or from the concurrent use of MAO inhibitors include confusion and restlessness, tremor, tachycardia, hypertension, clonus and hyperreflexia, shivering, and diaphoresis, as summarized by Boyer and Shannon. The long list of other medications, when used concurrently with SSRIs can produce the syndrome (including “triptans” for migraine), are noted in this reference.
The treatment is discontinuation of the medication, reduction of temperature and hypertension, benzodiazepines to control agitation, and in severe cases, the addition of cyproheptadine, a 5-HT2A receptor blocker. The typical dose is 4 to 8 mg every 4 to 6 h (or a higher initial dose); tablets are crushed and administered by nasogastric tube. Atypical antipsychosis agents with similar serotonin antagonist activity have also been used as treatment (olanzapine, chlorpromazine).
The discovery of the therapeutic effects of lithium salts in mania has led to its widespread use in the treatment of bipolar disease (bipolar disorder). The drug has proved relatively safe and blood levels are easily monitored. Its value is much more certain in treatment of the manic phase of bipolar disorder and prevention of recurrences of cyclic mood shifts than it is in treatment of anxiety and depression. Guidelines for the clinical use of lithium are given in Chap. 48. Its mechanism of action is unclear but there is experimental evidence that lithium blocks the stimulus-induced release of norepinephrine and dopamine and enhances the reuptake of this amine—the opposite in a sense, of what occurs with the other classes of antidepressants.