Antipsychotic drugs antipsychotics efficacy

Principally because of its efficacy/tolerability ratio, prescriptions for quetiapine are growing faster than for any other atypical antipsychotic drug at present (personal communication, Astra Zeneca). 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Describe the historical origins of the first antipsychotic drug chlorpromazine, and evaluate the evidence for its efficacy. 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

Some clinicians adhere to the maxim never use two drugs when one will suffice and will prefer amoxapine. This is a reasonable strategy. However, amoxapine may be difficult for many patients to tolerate, and using a combination of two drugs may afford the clinician a finer ability to determine the amount of antipsychotic to the doses of the antidepressant and the antipsychotic for maximum efficacy and minimum toxicity. 

Furthermore, clinical trials are performed in various cultural and geographical settings. Transcultural differences may play a significant role in drug efficacy e.g. oriental populations require much lower doses of antipsychotic drugs compared with Caucasian patient populations. Phase IV trials also may be performed to explore possible novel uses for compounds approved and marketed in other indications (e.g. treatment of anxiety disorders with antidepressants, treatment of bipolar disorder with anticonvulsants, etc.). 

Finally, there has been considerable interest in the use of vitamin E to combat EPS, including TD, based on the oxidative-stress hypothesis. A randomized trial of 12 patients receiving supplementary vitamin E and haloperidol versus 12 receiving haloperidol alone revealed that vitamin E had no prophylactic effect on acute drug-induced EPS, nor did it interfere with the antipsychotic s therapeutic efficacy ( 455). 

Analogous to the recent progress in antidepressant and antipsychotic drug therapy development the pharmacotherapy of bipolar disorder is also experiencing major advances. Data on the efficacy of mood stabilizers for bipolar disorder focus on the following ... 

This observation is a rare phenomenon in pharmacology. Meta-analyses of studies comparing various standard antidepressants for major depressive disorder reveal that all are equally efficacious (see Chapter 7). Similarly, meta-analyses of studies comparing antipsychotics find all equally efficacious for psychotic disorders (see Chapter 5). It is unusual to find a subclass of drugs more efficacious than others in the same class. Hence, if some antidepressants are clearly more effective than other antidepressants in OCD, it is truly noteworthy. 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Pimozide and molindone are typical antipsychotic drugs. There is no significant difference in efficacy between these newer typical and the older typical... 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

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