Antipsychotic drugs response time

Fig. 1. Principle of calculation of genotype-based dose adjustments based on differences in pharmacokinetic parameters, such as clearance and area under the curve. The theoretic dosages for genetic subgroups of poor (PMs), intermediate (IMs), extensive (RMs), and ultrarapid metabolizers (UMs) are depicted as schematic genotype-specific dosages to obtain equal plasma concentration time courses. C, concentration T, time. (From Kirchheiner J, Nickchcn K, Bauer M, et al. Pharmacogenetics of antidepressants and antipsychotics the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004 9(5) 442-73 with permission.)...

Generally, one drug should be started at a time so that its results can be evaluated. Occasionally, emergency or practical considerations dictate starting more than one drug simultaneously, but later one can undergo a therapeutic discontinuation (e.g., antipsychotic plus mood stabilizer in a severe manic episode). While the addition of several medications does occur, we emphasize that the clinician should evaluate and document the patient s response to each newly added medication. 

Perhaps in response to growing professional and public criticism, psychiatrists have become much more reluctant to publish criticism of any treatments or to mention their brain-disabling effects. Nowadays the neuroleptic drugs are always described as having a specific antipsychotic effect, rather than a numbing, lobotomy-like deactivation effect. In the words of my research assistant, Ian Goddard, This remarkable difference between historic and contemporary commentary on the effects of neuroleptics clearly reveals the existence of an all-pervasive denial that has consumed the profession in modern times (2007, unpublished). 

It is unquestionable that current antipsychotic therapy is comparatively effective and at the same time disappointingly insufficient. These drugs can treat the symptoms of the disorder but certainly do not provide a cure. The great majority of patients will have between 20 and 50% reduction in symptom severity. Some will have marked improvement beyond these figures, although this is rare, and a small minority of patients will be entirely refractory to all forms of treatment currently available. Full results from antipsychotic therapy take considerable time (although initial effects on some positive symptoms can be seen in a few days). Whereas the effect of benzodiazepines on anxiety and sleep can be measured in hours, and that of antidepressants in weeks, the full impact of antipsychotic therapy is measured in months. A study by Robinson et al. (1999) showed that only 20% of patients responded after 4 weeks of treatment with conventional antipsychotics, whereas after 26 weeks the number of responders had grown to about 70%. Similar results were reported with clozapine treatment, where a response was observed in 40% of subjects after 4 weeks and in 60% of subjects by week 17 (Kane et al., 2001). Clinical observations clearly show that improvement in... 

At any time, consider adding an antipsychotic agent (preferably a second-generation drug) if the patient is dangerously psychotic, aggressive, or with known good previous response to antipsychotics. 

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