Loxapine schizophrenia

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

Loxapine is a more expressed, active antipsychotic than chlorpromazine. Its sedative effect is inferior to that of chlorpromazine. Indications for its use and side effects correspond with those of phenothiazine derivatives. Loxapine is used for treating psychotic disturbances, in particular cases of chronic and severe schizophrenia. Synonyms of this drug are loxapac and loxitane. 

In a similar study, Petrie et al. (1982) studied the effectiveness of halo-peridol and loxapine in the same type of patients. The conclusion was that, although the improvement of the psychotic symptomatology was evident, the global improvement of life quality was not that evident. The authors suggested that the medication response in elderly patients with dementia and psychotic symptoms was much inferior to the one observed in young patients with schizophrenia. R. Barnes et al. (1982) carried out a similarly designed study and found an improvement in only one-third of the treated patients. However, that sample was oriented not only to psychotic symptoms (delusions and hallucinations) but also to disruptive behaviors in general. 

Haloperidol is the best-studied antipsychotic medication in children and adolescents with schizophrenia. In a double-blind, placebo- and active-controlled study, haloperidol (2 to 16 mg per day) and loxapine (10 to 200 mg per day) were equally effective and superior to placebo ( 168). This finding was replicated in a placebo-controlled, crossover study of haloperidol (doses of 0.5 to 3.5 mg per day or 0.02 to 0.12 mg/kg per day) in children 5.5 to 12 years of age ( 169). In this study, haloperidol was more effective than placebo in reducing ideas of reference, persecutory ideas, hallucinations, and thought disorder. 

Beside clozapine, only the 2-Cl-dibenzoxazepine loxapine (launched in 1975 by Wyeth) and 2-Cl-dibenzothiepine zotepine (launched in 1982 by Fujisawa) were introduced into clinical practice for the treatment of schizophrenia. Interestingly, in contrast with other dibenzodiazepines, all of which have a piperazinyl substitution at position-11, zotepine (which is a dibenzothiepine) has a 2-dimethylami-noethoxy-substitution at the same position. 

After 6 and 12 weeks of treatment with loxapine, patients with schizophrenia (n = 24 aged 18-70 years) showed both lymphocyte D2 dopamine-like and 5HT2a platelet receptor binding down-regulation, which suggests that both receptors are involved in the mechanism of action of the drug, as well as its possible extrapyramidal adverse effects (1). 

Singh AN, Barlas C, Saeedi H, Mishra RK. Effect of loxapine on peripheral dopamine-like and serotonin receptors in patients with schizophrenia. J Psychiatry Neurosci 2003 28 39-47. 

Fenfon M, Murphy B, Wood J, Bagnall A, Chue P, Leifner M. Loxapine for schizophrenia. Cochrane Dafabase Sysf Rev 2000 (2) CD00f943. 

Loxapine is used to treat and control the psychotic symptoms of both acute and chronic schizophrenia. Other uses include treatment of dementia, anxiety neurosis, hostile/aggressive behavior, and psychotic depression. 

Several newer drugs of varied beterocyclic structure are also effeetive in schizophrenia, ineluding elozapine, loxapine, olanzapine, molindone, pimozide, risperidone, quetiapine, and sertindole. In some cases, these atypical antipsychotic drugs have proved to be more effective and less toxic than the older drugs. However, they are much more eostly than standard drugs, most of whieh are preseribed generically. 

Citrome L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder focus on inhaled loxapine as an alternative to irq ectable agents. Ther Chn Risk Manag 2013 9 235 45. 

Keating GM. Loxapine inhalation powder a review of its use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. CNS Drugs 2013 27(6) 479-89. 

Moore, D. F. (1975) Treatment of acute schizophrenia with loxapine succinate (loxitane) in a controlled study with chlorptomazine. Curr. ther. Res., 18, 172. 

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