1. Tardive Dyskinesia: Between 10 to 20 percent of patients receiving antipsychotic agents develop some degree of tardive dyskinesia. It is now known that many cases of tardive dyskinesia are reversible and that many cases do not progress. Early signs of tardive dyskinesia are mostly seen in the area of the face. Movements of the tongue inside the buccal cavity that consist of retraction of the tongue on its longitudinal axis or irregular rotation around the longitudinal axis, with frequent movements in lateral directions, are thought to be the earliest signs. Choreoathetoid movement of the fingers and toes may also be observed, as may respiratory dyskinesia associated with irregular breathing and, perhaps, grunting.

   Tardive dyskinesia is thought to result from dopamine receptor supersensitivity following chronic receptor blockade by the antipsychotic agent. Anticholinergic drugs do not improve tardive dyskinesia and may make it worse. The recommended treatment of tardive dyskinesia is to lower the dosage of antipsychotic drugs and hope for gradual remission of the choreoathetoid movements. Increasing the dosage of an antipsychotic briefly masks the symptoms of tardive dyskinesia, but symptoms will reappear later as a reflection of the progression of receptor supersensitivity.

2. Neuroleptic Malignant Syndrome: Antipsychotic agents potentiate anticholinergic drugs, and toxic psychosis may occur. This confusional state usually appears early in treatment and, more commonly, at night and in elderly patients. Withdrawal of the offending agents is the treatment of choice. Antipsychotic drugs often interfere with body temperature regulation. Therefore, in hot climates this situation may result in hyperthermia and in cold climates hypothermia.

   The neuroleptic malignant syndrome is an exceedingly rare but potentially fatal condition characterized by parkinsonian-type rigidity, increased temperature, and altered consciousness. The syndrome is ill-defined and overlaps with hyperpyrexia, parkinsonism, and neuroleptic-induced catatonia. Coma may develop and result in rare terminal deaths. This syndrome is reported most often in young males, may appear suddenly, and usually lasts 5 to 10 days after cessation of neuroleptics. There is no treatment; therefore, early recognition and discontinuation of antipsychotic drugs, followed by supportive therapy, are indicated.

3. Hypersomnia And Lethary: Many patients on antipsychotic drugs sleep 12-14 hours per day and develop marked lethary. Often these side-effects disappear when treated with the newer serotonergic antidepressants (e.g., fluoxetine, trazodone). These antidepressants usually are given for 6 or more months.

4. Other Side-Effects: Depressed S-T segments, flattened T-waves, U-waves, and prolonged Q-T intervals may be caused by antipsychotic drugs. This situation is cause for concern, is more liable to occur with low potency agents, particularly thioridazine, and could increase vulnerability to arrhythmia.

   It is not possible to say to what extent antipsychotic drugs are involved in sudden death. Serious reactions to antipsychotic drugs are rare. Photosensitivity reactions are most common with chlorpromazine; vulnerable patients should wear protective screens on their exposed skin.

   Pigmentary retinopathy is associated with thioridazine and may impair vision if not detected. This complication occurred at dosages below the considered safe limit of 800 mg. Dosages of above 800 mg are, therefore, not recommended.

   Antipsychotic agents may affect libido and may produce difficulty in achieving and maintaining erection. Inability to reach orgasm or ejaculation and retrograde ejaculation have been reported. Antipsychotics also may cause amenorrhea, lactation, hirsutism, and gynecomastia.

   Weight gain may be more liable to occur with any antipsychotic drug which causes hypersomnia and lethargy. Onset of diabetes is another problem associated with atypical antipsychotics.

   Studies suggest that many antipsychotic drugs taken during pregnancy do not result in fetal abnormalities. Because these agents reach the fetal circulation, they may affect the newborn, thus producing postnatal depression and also dystonic symptoms.

"Drug Holidays" From Antipsychotic Medications

It was once thought that patients should take a "drug holiday" by periodically stopping their antipsychotic drugs for a few weeks every year. This practice is no longer recommended. Research has shown that these "drug holidays" increase the risk of relapse of schizoaffective disorder, as well as increase the risk of tardive dyskinesia.

Antidepressant Medications for Schizoaffective Disorder

The older (tricyclic) antidepressants often worsen schizoaffective disorder. However, the newer (serotonergic) antidepressants (e.g., fluoxetine, trazodone) have dramatically benefited many apathetic or depressed schizoaffective patients.