In this interdisciplinary, collaborative QI project, patients whose anticholinergic burden was reduced experienced a significant improvement in side effects, memory, and quality of life.

Treatment refractory schizophrenia is a serious issue affecting at least 30% of all patients with schizophrenia despite the continued emergence of new agents aimed at treating this disease. Clozapine therapy remains the most efficacious treatment for patients with schizophrenia who have failed two prior antipsychotics or those deemed an imminent harm to themselves or others. Because data are lacking on how to proceed if a patient should prove nonresponsive to clozapine therapy, the utmost care should be taken to ensure the optimization of clozapine. Therapeutic drug monitoring (TDM) is used with many other psychoactive agents to ensure the optimal therapeutic efficacy while minimizing adverse effects. The unique pharmacology of clozapine and the inter- and intraindividual variations in its pharmacokinetics make it a difficult agent with which to use TDM. The consensus is that 350 ng/mL is the lower threshold of therapeutic efficacy to define an adequate trial of clozapine. As of this writing, no clearly defined threshold exists for the upper limit of therapeutic efficacy or toxicity. TDM of clozapine can be useful in the following circumstances: when a clozapine-induced central nervous system toxicity is suspected, a medication that can inhibit or induce the metabolism of clozapine is being added or withdrawn, a change in smoking status has occurred, concerns for medication nonadherence are present, or decompensation while on a previously effective clozapine dosage is observed. The psychiatric pharmacist may play a crucial role in the interpretation and effective utilization of serum clozapine and norclozapine levels. This review will examine the current evidence for the clinical utility of monitoring serum levels of clozapine and its metabolites.

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A variety of somatic therapies can be used to treat individuals suffering from psychosis. Most commonly, providers will prescribe antipsychotics, which generally block dopamine receptors and are particularly useful at reducing positive symptoms. Second-generation antipsychotics have fewer movement side effects than older agents do, but they are more expensive and have more metabolic side effects. Long-acting injectable (LAI) antipsychotics can be useful for improving outcomes, especially in non-adherent patients, and clozapine is the gold standard for treatment-refractory psychosis. Other agents may be useful for adjunct therapy, or in early psychosis, such as antidepressants, mood stabilizers, and benzodiazepines. In this chapter, we will also review other somatic therapies such as electroconvulsive therapy (ECT) and other neuromodulation approaches.