Past and Present Progress in the Pharmacologic Treatment of Schizophrenia

Albert Einstein College of Medicine, New York, New York, United States
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 09/2010; 71(9):1115-24. DOI: 10.4088/JCP.10r06264yel
Source: PubMed


Despite treatment advances over the past decades, schizophrenia remains one of the most severe psychiatric disorders that is associated with a chronic relapsing course and marked functional impairment in a substantial proportion of patients. In this article, a historical overview of the pharmacologic advances in the treatment of schizophrenia over the past 50 years is presented. This is followed by a review of the current developments in optimizing the treatment and outcomes in patients with schizophrenia. Methodological challenges, potential solutions, and areas of particular need for further research are highlighted. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field must advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate regarding whether and which first- or second-generation antipsychotics should be used. However, especially when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes cannot be upheld, and a more differentiated view and treatment selection are required. The desired, individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Acute and long-term goals and effects of medication treatment should be balanced. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To discover novel treatments with enhanced/broader efficacy and improved tolerability, and to enable personalized treatment, the mechanisms underlying illness development and progression, symptomatic improvement, and side effect development need to be elucidated.

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    • "Although antipsychotic agents are the mainstay in treating schizophrenia , their clinical use is largely limited owing to undesirable side effects that often result in discontinuation and relapse (Kane and Correll, 2010; Warnez and Alessi-Severini, 2014). This has led to a demand for the development of alternative strategies to improve medication compliance and antipsychotic response. "
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    • "chlorpromazine, promethazine and thioridazine. These derivatives have also excellent antipsychotic and antiemetic activities, although they may possibly give rise to serious side effects, such as extrapyramidal symptoms, including akathisia and tardive dyskinesia, hyperprolactinaemia, and the scarce but potentially mortal neuroleptic malignant syndrome as well as substantial weight gain [11] [12] [13]. Moreover, phenothiazine derivatives are employed as inodilator in congestive heart failure, acting upon the phosphodiesterase I; and chlorpromazine and prochlorperazine are especially exploited in emergency rooms to cure migraine and other intractable headaches [14] [15]. "
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    • "The onset of schizophrenia is typically in late adolescence or early adulthood, and includes distinctive symptoms, commonly referred to as positive, negative, and cognitive. To date, effective treatments for schizophrenia have been limited to medications with antidopaminergic activity, which alleviate symptoms by augmenting dysfunctional neurotransmitter systems.2 While antipsychotics are most effective for positive symptoms, negative and cognitive symptoms are less well addressed.3 "
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