First Generation Antipsychotic Agents

When Emil Kraepelin first described the concept of schizophrenia over a century ago, he asserted: "The treatment of dementia praecox offers few points for intervention." The introduction of electroconvulsive therapy in 1938 provided the first somewhat efficacious somatic treatment of schizophrenia; prior to that time, good treatment consisted of providing the afflicted patient with a safe and supportive environment in the form of a long-term psychiatric hospitalization. Chlorpromazine was the first neuroleptic to be introduced into clinical practice. Discovery of its "tranquilizing" effects in 1952 (Delay and Deniker, 1952) led to the development of the first generation of antipsychotic medications, which constituted the primary pharmacological treatment of schizophrenia for the next 40 years. Approximately 30 such "typical" or "conventional" antipsychotics have been developed; 15 such agents are approved as antipsychotics in the United States. These medications have been very effective in establishing and maintaining remission of acute episodes of the illness, primarily by controlling positive symptoms;

Evolution Antipsychotics
Figure 10.1. Antipsychotic therapy.

they are relatively ineffective, however, in treating the negative, cognitive, and mood symptom domains of schizophrenia. Furthermore, even with regard to positive symptoms, conventional antipsychotics are only partially effective in about 40 percent of patients, and completely ineffective in another 20 percent. While these medications [chlorpromazine (Thorazine), trifluoperazine (Stelazine), thioridazine (Mellaril), thiothixene (Navane), haloperidol (Haldol), etc.] differ from one another in potency and side effect profile, they have similar overall efficacy, and all cause significant EPS and tardive dyskinesia. EPS have a pervasive negative impact on treatment, contributing to dysphoria and poor compliance, worsening of negative symptoms and cognitive function, and increased risk of tardive dyskinesia. While appropriate use of lower doses of these agents can reduce these adverse effects, EPS and its consequences constitute the major limitation of first-generation antipsychotics (Casey, 1995; Jibson and Tandon, 1998).

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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