Pharmacotherapy of treatment-resistant schizophrenia: a clinical perspective.

A significant number of patients with schizophrenia do not respond adequately to an initial antipsychotic trial. As first step within a treatment algorithm for therapy-refractory schizophrenia 'pseudoresistance' should be ruled out (eg, re-evaluation of the diagnosis, comorbidities, compliance and adherence in terms of medication intake, adequate dose and treatment duration, and achievement of sufficient plasma levels). In case of treatment resistance, two strategies that are often used in clinical routine care contain dose increase of the current administered antipsychotic drug (dose escalation, high-dose treatment) and switch to another, new antipsychotic. Although the response rates for both options are generally rather low, we see from the evidence-based perspective a slight advantage of the switching strategy (preferably to an antipsychotic with a different receptor-binding profile) compared to a high-dose treatment. After treatment failures with at least two different antipsychotic drugs, a monotherapy with clozapine is considered to be the treatment option of first choice. At present, pharmacological combination and augmentation strategies cannot be regarded as a generally recommendable evidence-based treatment method. Antipsychotic monotherapy should be preferably sought. In case of combination treatment, it appears more appropriate to combine preferentially two antipsychotics with different receptor-binding profiles. Augmentation of antipsychotics with other agents should be used primarily to treat specific target symptoms.