First-generation antipsychotics

Compared to the older antipsychotics (first-generation antipsychotics), the more recently developed second-generation antipsychotics are associated with a lower risk of motor side effects (tremor, stiffness, restlessness, and dyskinesia) may offer greater benefits for affective, negative, and cognitive symptoms and may prolong the time to psychotic relapse. 

TABLE 34-6. First-Generation (Typical) Antipsychotic Dosing of Decanoate Preparations... 

TABLE 34-7. Side Effects of First-Generation (Typical) Antipsychotics... 

Chlorpromazine equivalents Approximate dose equivalent of a first-generation antipsychotic to 100 mg of chlorpromazine (relative potency). 

It is clear that ethnic differences in response to antipsychotics exist (Emsley et al, 2002 Frackiewicz et al, 1997). Whereas there has been some work examining first-generation antipsychotics (FGAs) (for reviews, see Frackiewicz etal, 1997 Poolsup et al, 2000), there remains a considerable dearth of research that has examined ethnic differences with respect to the second-generation antipsychotics (SGAs). 

Current antipsychotics used to treat patients are divided into two classes the first generation antipsychotics (FGA) or typicals (e.g., chlorproma-zine, haloperidol, thioridazine, and loxapine) and the second generation antipsychotics (SGA) or atypicals (i.e., clozapine, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, and asenapine). 

Increased ventricular size, decreased brain size, and brain asymmetry have been reported. Lower hippocampal volume may correspond to impairment in neuropsychological testing and poorer response to first-generation antipsychotics (PGAs). 

Drug (o/o) (hours) Selected first-generation antipsychotics (FGAs) Pathways Active Metabolites... 

Other first generation (atypical) antipsychotics include thioxanthenes, haloperidol, pimozide, and loxapine. 

The first of the second-generation, or atypical, antipsychotics was clozapine. Clozapine (Clozaril) is relatively free of the movement disorders that characterize the first-generation drugs. This is true of, and defines, second-generation, atypical antipsychotics. It was a significant breakthrough for schizophrenia patients. 

EPS include acute dystonic reactions, parkinsonian syndrome, akathisia, tardive dyskinesia, and neuroleptic mahgnant syndrome. Although high-potency conventional antipsychotics are more hkely than low-potency conventional antipsychotics to cause EPS, all first-generation antipsychotic drugs are equally hkely to cause tardive dyskinesia. The atypical antipsychotics cause suhstantially fewer EPS, which is one reason that they are recommended as first-line agents. 

Drugs commonly causing this First-generation antipsychotics... 

The first generation antipsychotics, now known as typical drugs, were all D2 receptor blockers and, as such, very likely to produce Parkinsonian side effects. Because antipsychotic potency was associated with D2 receptor affinity, it was assumed that dopamine overactivity was the essential defect in schizophrenia and that a direct dopamine blockade was the definitive route to treatment. But these drugs affected both the target dopamine pathways of the mesolimbic projection and the uninvolved nigrostriatal projection. Unfortunately, that meant that movement disorders were the price that had to be paid for antipsychosis. 

Coveil NH, Weissman EM, Essock SM. Weight gain with clozapine compared to first generation antipsychotic medications. Schizophr Bull 2004 30 229-40. 

Unfortunately, these drugs—especially the first generation of antipsychotics introduced in the 1950s—have side effects similar to those seen in patients with Parkinson s disease tremors when at rest, reduction of voluntary movement, muscle spasticity and dystonia, or sustained muscle contractions. These symptoms confirm the role of dopamine neurons in the initiation and control of movement. Antipsychotic drugs also block dopamine receptors within a region of the brain that controls... 

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