Chronic Antipsychotic Therapy Research Articles

Antipsychotics and anesthetic drugs

Psychiatric illness is common, affecting up to 10% of the population, with around 1% diagnosed with a major psychiatric disorder. An increased mortality rate in the postoperative period for schizophrenic patients receiving chronic antipsychotic therapy has been demonstrated. According to the Diagnostic and Statistical Manual of Disease, schizophrenia-associated psychotic disorders are characterized by disturbances in emotional, behavioral and cognitive arenas, impeding on nearly every aspect of life functioning in the form of thought disorders, delusions and hallucinations. Chronic schizophrenic patients lack pain sensitivity, and have pituitary-adrenal and autonomic nerve dysfunction, abnormalities of the immune system, and water intoxication. These alterations may influence postoperative outcome. Psychotropic drugs often given in combination with each other or with other non-psychiatric drugs generally exert profound effects on the central and peripheral neurotransmitter and ionic mechanisms. The increased complications are associated with physical disorders, antipsychotic or hazardous health behaviour and interactions between antipsychotics and anaesthetic drugs. Adverse responses during anaesthesia include arrhythmias, hypotension, prolonged narcosis or coma, hyperpyrexia, post-operative ileus and post-operative confusion. Although drug interaction probably remains the most potentially serious problem current evidence suggests that psychiatric medication need not be discontinued prior to anesthesia.

Dry Eye and Antipsychotic Drug

Background: To study the dry eye prevalence in patients on chronic antipsychotic therapy.
 Methods: 50 patients who were diagnosed of schizophrenia and have been under anti-pschyotic were included. 
 Results: 17 patients out of 50 patients on anti-psychotic medications for more than 2 years had dry eye disease. Of the 100 eyes evaluated, 30 eyes were found to have dry eye disease. Patients on two drug regimen showed more prevalence of dry eye than on mono drug regimen in our study.
 Conclusion: Anti-psychotic drug may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities.
 Keywords: Dry eye, Prevalence, Antipsychotic

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment.

Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.

Emerging pharmacological therapies in schizophrenia: what's new, what's different, what's next?

There are several new and emerging medication interventions for both the acute and maintenance treatment phases of schizophrenia. Recently approved are 2 new dopamine receptor partial agonists, brexpiprazole and cariprazine, as well as 2 new long-acting injectable antipsychotic formulations, aripiprazole lauroxil and 3-month paliperidone palmitate. Although differences in efficacy compared to other available choices are not expected, the new oral options offer different tolerability profiles that may be attractive for individual patients who have had difficulties with older medications. The new long-acting injectable options provide additional flexibility in terms of increasing the time interval between injections. In Phase III of clinical development is a novel antipsychotic, lumateperone (ITI-007), that appears to have little in the way of significant adverse effects. Deutetrabenazine and valbenazine are agents in Phase III for the treatment of tardive dyskinesia, a condition that can be found among persons receiving chronic antipsychotic therapy. On the horizon are additional injectable formulations of familiar antipsychotics, aripiprazole and risperidone, that may be more convenient than what is presently available.

Strategies to control antipsychotic-induced weight gain

To the editor: the recent article by Han et al. about the short and long term effects of antipsychotic drug treatment on weight gain and H1 receptor expression was highly interesting (Han et al., 2008). Interestingly, a number of new pharmacological as well as behavioral strategies for managing antipsychotic-induced weight gain have emerged over the past few years. For instance, Levy et al. in a recent study have shown that topiramate can be effectively used for controlling weight gain in schizophrenic patients on chronic anti psychotic therapy (Levy et al., 2007). Bupropion is another medication that is effective in reducing antipsychotic-induced weight gain. For instance, the average weight loss after the addition of bupropion is about 3.4 kg (Gadde et al., 2006). Similarly, replacement therapy with melatonin reduces weight gain secondary to the use of anti psychotics such as olanzapine (Raskind et al., 2007). The effectiveness of metformin in the management of antipsychotic-induced weight gain has been re confirmed in recent studies conducted by Wu et al. (Wu et al., 2008). Other drugs that have also been shown to be effective include acetazolamide andmemantine. In addition, the simultaneous use of behavioral therapies may make the pharmacological weight control strategies more effective. For instance, Khazaal et al. have recently demonstrated the effectiveness of cognitive behavioral therapy in controlling weight gain in patients on chronic anti psychotic therapy (Khazaal et al., 2007). Clearly, antipsychotic-induced weight gain is a major problem in patients on psycho-pharmacological agents. Hopefully, increased awareness amongst clinicians and

Possible anti-oxidant and neuroprotective mechanisms of zolpidem in attenuating typical anti-psychotic-induced orofacial dyskinesia—A biochemical and neurochemical study

Tardive dyskinesia is a serious motor side effect of chronic anti-psychotic therapy. The pathophysiology of this disabling and commonly irreversible movement disorder continues obscure and may be caused due to GABAergic hypofunction or increased oxidative damage and free radical generation. Chronic treatment with typical antipsychotics leads to the development of abnormal hyperkinetic orofacial movements (vacuous chewing movements, tongue protrusions and facial jerking) in rats and is widely accepted as the animal model for tardive dyskinesia. Zolpidem, a GABA-mimetic drug is structurally related to melatonin and has been reported to possess anti-oxidant and neuroprotective effects both in vivo and in vitro. The study was carried out to investigate whether zolpidem can be used in the treatment of typical anti-psychotic-induced orofacial dyskinesia. Chronic haloperidol (1 mg/kg, i.p. for 21 days) and chlorpromazine (5 mg/kg, i.p. for 21 days) treatment significantly induced orofacial hyperkinetic movements and zolpidem [ N, N, 6-trimethyl-2- p-tolyl-imidazo (1, 2- a) pyridine 3-acetamideL-(+)] dose dependently (1, 2, 5 mg/kg i.p. for 21 days) reduced these haloperidol and chlorpromazine-induced hyperkinetic orofacial movements. Biochemical analysis revealed that haloperidol and chlorpromazine treatment significantly induced increase in lipid peroxidation and decrease in the levels of total nitric oxide levels, non-protein thiols (NPSH) and of anti-oxidant defense enzymes, superoxide dismutase (SOD) and catalase in the striatum of rat brain. Co-administration of zolpidem (1, 2, 5 mg/kg i.p. for 21 days) significantly reduced the lipid peroxidation and restored the non-protein thiols and total nitric oxide levels induced by chronic haloperidol and chlorpromazine treatment. It also significantly reversed the haloperidol and chlorpromazine-induced decrease in brain SOD and catalase activity. Neurochemical analysis (Neurotransmitter and their metabolite level estimation) revealed that haloperidol and chlorpromazine significantly decreased the dopamine, norepinephrine and serotonin levels in brain homogenates where as it caused a significant increase in the metabolite (VMA and HVA) levels in urine, which were significantly reversed by zolpidem at higher doses. Result of the present study support the therapeutic use of zolpidem in the treatment of typical anti-psychotic-induced orofacial dyskinesia.

Bone Mineral Density in Male Schizophrenia Patients: A Review

Decreased bone mineral density (BMD) has been documented frequently in female patients with schizophrenia receiving antipsychotic therapy with potent dopamine D(2) antagonists, but there has been much less coverage of this issue in male patients with schizophrenia despite the fact that older males who sustain osteopenia-related hip fractures have subsequently greater mortality than females. A Medline search was performed for the years 1966-2004 using the following search terms: "osteopenia or osteoporosis or bone density or bone mineral density," combined with "schizophrenia or psychosis or antipsychotic." The search yielded 8 studies which provided data on bone mineral density in male patients with schizophrenia, of which 2 were case reports, and 3 were controlled studies. Hormonal measures were present in 6 studies. In every study where such information was provided, the patients with schizophrenia had significantly lower BMD than nonschizophrenic controls or population norms, with the prevalence of osteopenia ranging from 40-72%. Low BMD and corresponding osteopenia or osteoporosis may be a highly prevalent but significantly underdiagnosed medical condition among male schizophrenia patients. Psychiatrists should consider BMD screening among older males who have received chronic antipsychotic therapy with antipsychotics expected to achieve high levels of postsynaptic D(2) antagonism.

Acute Dystonic Reaction and the Neuroleptic Malignant Syndrome

Up to 90% of patients on chronic antipsychotic therapy will experience adverse neurologic side effects, with many of these effects attributable to the dopamine-blocking properties of these drugs. Even the newer, “atypical” antipsychotics are increasingly associated with neurologic complications. In the acute care setting, these medications have broad application beyond the management of psychiatric illness. Given the extent of their use, clinicians should be familiar with the spectrum of neurological syndromes that can develop. Some are common, such as akathisia, acute dystonic reaction, tardive dyskinesia, and drug-induced parkinsonism. Others, such as the life-threatening neuroleptic malignant syndrome, are rare yet must be recognized early to affect survival and improve outcome. This discussion highlights 2 idiosyncratic syndromes, acute dystonic reaction and neuroleptic malignant syndrome. The differential diagnosis for both syndromes and their management is discussed.

Depressed pituitary-adrenal response to surgical stress in chronic schizophrenic patients.

We evaluated whether pituitary-adrenal response to surgical stress is modified in chronic schizophrenic patients. Twenty-two schizophrenic patients on chronic antipsychotic therapy of phenothiazine derivatives over 10 years underwent orthopedic surgery of the extremities under general anesthesia by isoflurane and nitrous oxide. In chronic schizophrenic patients, responses of plasma epinephrine, norepinephrine, ACTH and cortisol levels during surgical stress were significantly lower than those of control patients. The attenuated response to surgical stress in these patients may be associated with their autonomic dysfunction and decreased pituitary-adrenal activity due to chronic administration of antipsychotic agents.

Up-regulation of D3 dopamine receptor mRNA by neuroleptics

The effects of 14 days neuroleptic treatment on the expression of the D3 dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D3 mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D3 expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D3 expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D3 receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D3 receptor up-regulation in the striatum.

Prevalence of dystonia in veterans on chronic antipsychotic therapy

The prevalence of dystonia was studied in 125 veterans on chronic antipsychotic therapy using a detailed and systematic examination. Twenty-seven out of 125 had dystonic manifestations. The most common areas involved were hands and jaw. There was no relation between the presence or absence of dystonia, and duration of neuroleptic therapy. There was a tendency for tardive akathisia to occur more frequently in patients with dystonia than in those without it (Fisher's exact probability test, p = 0.0656). Tardive dystonia in its milder forms may be more common than currently believed.