Atypical neuroleptics/antipsychotics

Roberts, D.C.S., and Vickers, G. Atypical neuroleptics increase selfadministration of cocaine An evaluation of a behavioral sereen for antipsychotic activity. Psychopharmacology 82 135-139, 1984. 

Roberts D., Vickers G. Atypical neuroleptics increase self-administration of cocaine an evaluation of a behavioral screen for antipsychotic activity. Psychopharmacology. 82 1135, 1984. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

In the late 1980s, clozapine a chlorpromazine like compound with a multiplicity of effects was rediscovered and termed an atypical neuroleptic. It appears to be the only genuinely atypical agent - that is an agent with significant beneficial treatment effects in the absence of EPS (see Wahlbeck et ah, 1999). A second generation of antipsychotics have succeeded clozapine been marketed as being atypical. 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

Atypical neuroleptics. Because of the limited effectiveness and safety of conventional neuroleptics in TS, clinicians have turned to a new generation of neuroleptics that have been introduced for the treatment of schizophrenia. Risperidone, a member of a class of antipsychotics that blocks both DA and serotonin receptors, has been established as superior to placebo and equal, or superior, to haloperidol in the treatment of schizophrenia (Chouinard et al. 1993 Marder and Meibach 1994]. Risperidone has a more favorable side-effect profile than that of conventional neuroleptics and may have less potential for producing tardive dyskinesia. Compared with haloperidol, fewer extrapyramidal side effects are observed with risperidone in doses of 6 mg/ day or less. As encouraging reports appear in the literature (Lombroso et al. 1995 Stamenkovic et al. 1994 van der Linden et al. 1994], risperidone is currently being widely used by clinicians to treat tic disorders. 

Caroff SN, Mann SC, Campbell EC. Atypical antipsychotics and neuroleptic malignant syndrome. Psychiatr Ann 2000 30 314-321. 

FIGURE 7—35. Combination treatments for bipolar disorder (bipolar combos). Combination drug treatment is the rule rather than the exception for patients with bipolar disorder. It is best to attempt monotherapy, however, with first-line lithium or valproic acid, with second-line atypical antipsychotics, or with third-line anticonvulsant mood stabilizers. A very common situation in acute treatment of the manic phase of bipolar disorder is to treat with both a mood stabilizer and an atypical antipsychotic (atypical combo). Agitated patients may require intermittent doses of sedating benzodiazepines (benzo assault weapon), whereas patients out of control may require intermittent doses of tranquil-izing neuroleptics (neuroleptic nuclear weapon). For maintenance treatment, patients often require combinations of two mood stabilizers (mood stabilizer combo) or a mood stabilizer with an atypical antipsychotic (atypical combo). For patients who have depressive episodes despite mood stabilizer or atypical combos, antidepressants may be required (antidepressant combo). However, antidepressants may also decompensate patients into overt mania, rapid cycling states, or mixed states of mania and depression. Thus, antidepressant combos are used cautiously. 

Antipsychotic activity mescaline are antagonists at 5-HT2 receptors Many atypical neuroleptics (e.g. amperozide and risperidone) are 5-HT2 receptor antagonists. In animals, 5-HT3 antagonists have profiles similar to chronically... 

In experimental studies, many clinically effective neuroleptics have been shown to act as 5-HT2A receptor antagonists. Studies on post-mortem brain from schizophrenic patients have shown that the decrease in the number of 5-HT2A receptors in the prefrontal cortex might be related to the disease process. It therefore seems unlikely that the antipsychotic activity of neuroleptics can be explained solely in terms of their action on 5-HT receptors. Furthermore, no correlation exists between the average therapeutic doses of a neuroleptic and its affinity for 5-HT receptors. It does seem possible, however, that several atypical neuroleptics such as amperozide, risperidone and possibly ritanserin do owe at least part of the pharmacological profile to their ability to inhibit 5-HT receptors. 

Regarding neuroleptic-induced dystonias, it is well known that typical neuroleptics cause catalepsy in rats and movement disorders in man. By contrast, the atypical neuroleptics clozapine and sulpiride have a low propensity to cause movement disorders in man even though they have established antipsychotic effects. These atypical neuroleptics, unlike many of the typical neuroleptics, have a low affinity for sigma receptors which lends support to the hypothesis that the dystonias produced by typical... 

We will examine recent studies, some involving atypical neuroleptics, confirming that antipsychotic drugs shorten the life span. The production of a metabolic syndrome undoubtedly contributes to this increased risk of dying. However, this risk was also detected in regard to... 

To further examine the risk of atypical neuroleptics causing TD in children, Wonodi and a team from the Maryland Psychiatric Research Center (2007) followed up 118 children who had been taking neuroleptics, mostly atypicals, for at least 6 months. As a sign of the irrational overprescription of these drugs, only 19% of the children on antipsychotic drugs had ever displayed psychotic symptoms. 

Significant correlation between duration of atypical meds and NAA signal in ACC in patients on atypical antipsychotics typical neuroleptic users showed progressive decrease in NAA levels in ACC 4 NAA in ACC and fewer errors on Wisconsin Card Sort Task in patients treated with atypical meds compared with patients treated with typical antipsychotics 4 NAA/Cr in FL of children with schizophrenia spectrum disorders no medication effects or other metabolite differences found... 

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