Benzodiazepines antipsychotic action

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

Rather than raise the dose above these levels in acutely agitated patients requiring acute antipsychotic actions, consider augmentation with a benzodiazepine or conventional antipsychotic, either orally or intramuscularly... 

Benzodiazepines are preferred by many for the management of agitation in nonpsychotic bipolar patients, though antipsychotics are effective as well. The most widely used benzodiazepines for this purpose are lorazepam and clonazepam. Lorazepam is perhaps the most versatile of the benzodiazepines. It has an intermediate duration of action, does not tend to accumulate and thereby cause confusion or excessive drowsiness, and can be administered by mouth, intramuscular injection, or intravenous injection. Lorazepam should be administered on an as-needed basis several times daily at 0.5-2mg per dose. The calming effects of lorazepam are usually evident within 20-30 minutes and will last for several hours. 

Benzodiazepines. These medications are also known as minor tranquilizers. In general, they have been found less effective than antipsychotics in treating agitation over the long term. However, their relatively quick onset of action makes them effective for acute episodic agitation. 

Whereas antipsychotics and antidepressants are used mainly in major psychiatry , Le. in the treatment of schizophrenia and depression, anxiolytics are also used in general medicine for the treatment of neurotic, vegetative, psychosomatic and even purely physical conditions. This multiple usage is promoted by the fact that anxiolytics of the benzodiazepine type have an almost exclusively central action so that vegetative effects (dry mouth, sweating, visual disturbances, urine retention, constipation, fall in blood pressure), which can be unpleasant for patients or even hazardous, are practically absent. 

Some 25 anxiolytics and hypnotics are marketed at present the best known of these are listed in Table 1.10. Here, again., there are striking differences between the doses of these products, which can be explained m the same way as for antipsychotics. The benzodiazepine derivatives and related compounds show few qualitative differences nevertheless, the time effect features, i.e. the timing of onset of action and peak action as well as duration of action, mean that it is sensible to use different products for different purposes. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

It is not clear that so-called antipsychotic drugs are superior to other types of drugs with sedative effects but different mechanisms of action. Lithium, benzodiazepines and opium have been shown to be comparable to neuroleptics in the treatment of psychotic states in some studies. The ability of the neuroleptic drugs to reduce the most characteristic symptoms of psychosis such as hallucinations, delusions and thought disorder have often been interpreted as evidence of their specifically antipsychotic or antischizophrenic action (The National Institute of Mental Health Psychopharmacology Service Center Collaborative Study... 

The benzodiazepines have no antipsychotic activity, nor any analgesic action and do not affect the autonomic nervous system. All of the benzodiazepines exhibit the following actions to a greater or lesser extent ... 

Lithium is an alkaline earth element that is used medicinally in the form of salts such as lithium chloride and lithium carbonate. Its main use is in the prevention or attenuation of recurrent episodes of mania and depression in individuals with bipolar mood disorder (manic depression). Lithium also has clearly established antima-nic activity, although its relatively slow onset of action often necessitates the use of ancillary drugs, such as antipsychotic drugs and/or benzodiazepines, at the start of therapy. If lithium alone is ineffective for recurrent bipolar mood disorder, combining it or replacing it with car-bamazepine or valproate may be of value reports with lamotrigine and olanzapine are also encouraging. 

Due to delayed onset of action, lithium monotherapy may not be the first choice in acute mania, but rather may be used as an adjunct to atypical antipsychotics, benzodiazepines, and/or valproate loading... 

Indications and use. Lithium carbonate is effective treatment in > 75% of episodes of acute mania or hypomania. Because its therapeutic action takes 2-3 weeks to develop, lithium is generally used in combination with a benzodiazepine such as lorazepam or diazepam (or with an antipsychotic agent where there are also psychotic features). 

The pharmacology of benzodiazepine derivatives differs significantly from that of the neuroleptics, in that the benzodiazepines have no psychoplegic (antipsychotic) activity and cause no extrapyramidal, autonomic, or endocrine side effects. In addition, unlike the neuroleptics, which lower the seizure threshold, these substances are anticonvulsants. In addition, they are anxiolytics, muscle relaxants, and mild sedatives. Although the benzodiazepine derivatives do not produce pronounced autonomic or CV side effects, they can reduce or block the emotionally induced changes in cardiovascular functions, probably through actions on the limbic system. 

Introduction - As in previous years, molecular modification of known structures, especially in the tricyclic systems, has played an important part in the chemistry emd pharmacology of neuroleptic drugs. Most of the reported work on benzodiazepines was concerned with additional studies of compounds already undergoing clinical investigation. There appeared to be less emphasis on the chemistry and pharmacology of the carbamates and little new was added to the knowledge of mechanisms and modes of action of antipsychotic and anti-anxiety agents. 

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