The most appropriate treatment for this patient with schizophrenia is to switch his chlorpromazine to clozapine. His history and physical examination findings are suggestive of extrapyramidal symptoms, and tardive dyskinesia in particular. Extrapyramidal symptoms are drug-induced disorders of movement that usually occur with agents that block dopamine receptors. Although a number of different drugs may be associated with extrapyramidal symptoms, they are most frequently caused by first-generation antipsychotic medications (such as chlorpromazine) that antagonize D₂ dopamine receptors. Extrapyramidal symptoms typically include akathisia (a sense of motor restlessness with a compelling urge to move that makes it difficult to sit still), dystonia (continuous, involuntary spasms and contractions of major muscle groups), and parkinsonism (tremor, rigidity, and bradykinesia). Tardive dyskinesia is a specific form of extrapyramidal movement disorder that occurs with longer-term use (typically >1 month) of dopamine-blocking agents with variable findings of orofacial dyskinesia, facial grimacing, athetotic (slow, writhing) movements, and tics. Extrapyramidal symptoms are more common with first-generation antipsychotic agents compared with second-generation antipsychotic medications. Thus, switching to the second-generation antipsychotic clozapine would be the best option in this patient. A recent meta-analysis showed that clozapine was not only the least likely to cause extrapyramidal symptoms among antipsychotic agents, but was also the most effective drug. This patient also exhibits a significant amount of negative symptoms (flat affect, monotone speech, social withdrawal), which may respond better to a second-generation antipsychotic medication.

Continuing chlorpromazine would be inappropriate in this patient because tardive dyskinesia is a serious manifestation of extrapyramidal symptoms and may become untreatable if prolonged. Thus, the offending agent should be stopped as soon as possible.

Haloperidol has been shown to be significantly more likely to cause extrapyramidal symptoms than any other first-generation or second-generation antipsychotic medication; therefore, switching to haloperidol in this patient would not be appropriate.

Similarly, switching to another first-generation antipsychotic agent, thioridazine, would also likely not address his extrapyramidal side effects associated with therapy.