Pharmacotherapeutic treatment for schizophrenia – side effects, major interactions and contraindications

Important side effects

The side effects associated with specific antipsychotic drugs determine the choice of the drug for use in management of schizophrenia. Typical antipsychotic drugs are for instance associated with extrapyramidal symptoms such as subacute Parkinsonism, somnolence, dystonia and akathisia (Johnsen et al. 2010; Metzer 2003; Metzer 2002). Although, generally the atypical antipsychotics reduce such adverse effects, atypical antipsychotics such as quetiapine, risperidone, sertindole and olanzapine have also been associated with mild EPS symptoms, thus necessitating administration of anti-Parkinson’s medication (Leucht, Pitschel-Walz & Kissling 1999; Lindenmayer et al. 2007). Such adverse effects are thought to arise from the increase in cholinergic activity in the basal ganglia, due to an inhibitory effect of the D2-blockade on striatal cholinergic neurons (Metzer 2002).

Other side effects of antipsychotic medication have been their association with adverse cardiac effects, weight gain, glucose intolerance and dyslipidaemia (Ryan & Thakore 2002). Cardiac effects such as ventricular arrhythmia have been suggested to explain aspects such as sudden death resulting from an overdose of the antipsychotic drugs, since antipsychotics such as thioridazine block sodium channels and delay ventricular repolarization (Ryan & Thakore 2002). Antipsychotics also facilitate weight gain, with the extent of weight gain being related to the serotonergic, cholinergic and dopaminergic activities of specific drugs (Ryan & Thakore 2002). Although the mechanism is not well-elucidated, such weight gain is thought to be related to a reduced sensation of the CNS to leptin, a satiety hormone, which leads to increased appetite in individuals using such medication (Ryan & Thakore 2002). Such weight gain is further associated with the risk of developing obesity and diabetes mellitus, conditions that are prevalent in individuals suffering from schizophrenia (Ryan & Thakore 2002). Further, antipsychotics (e.g. olanzapine and clozapine) have been linked to the development of glucose intolerance in schizophrenics, a factor that also contributes to the development of diabetes mellitus (Ryan & Thakore 2002). Finally, treatment with antipsychotics is associated with increased blood lipid levels, with one study associating typical antipsychotics with high plasma levels of cholesterol in chronic schizophrenics, while clozapine led to increased plasma concentration of triglycerides in neuroleptic-resistant patients (Ryan & Thakore 2002).

Major interactions

The principal CNS effect of antipsychotic drugs renders them candidates for interactions with other centrally acting drugs. For instance, use of antipsychotics in combination with antihypertensives could increase the effect of such antihypertensive drugs, due to the independent hypotensive effect of antipsychotics; this would present a clinical challenge for patients at a risk of orthostatic hypotension (Weiden, 2012; de Leon et al. 2009). Other drugs such as carbamazepine, an enzyme inducer, could result into the low bioavailability of antipsychotics thus reducing their efficacy (de Leon et al. 2009). When used in combination with other drugs that compete for the same metabolic enzymes for elimination (e.g. CYP2D6 and CYP3A4), antipsychotics could lead to toxicity (Weiden, 2012; de Leon et al. 2009; Prior et al. 1998).


There are no absolute contraindications with regard to atypical antipsychotics but contraindications exist with regard to aspects such as hypersensitivity to specific antipsychotic agents (de Leon et al. 2009). Other contraindications relate to patients with a history of arrhythmia, for whom antipsychotics such as ziprasidone, which lengthen the QTc interval (a measure of the rate of ventricular depolarization and repolarization), are contraindicated (Ryan & Thakore 2002; de Leon et al. 2009). Further contraindications exist where risks outweigh benefits with regard to patients having liver damage, conditions expositing individuals to hypotension, severe cardiovascular disease and metabolic syndrome (de Leon et al. 2009). Go to concluding part here.

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