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OBJECTIVE This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses. METHODS The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RESULTS Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone). CONCLUSIONS LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

The authors note an apparent unawareness of, as well as a paucity of recent literature pertaining to, hyperpyrexia as a complication of psychotropic drug treatment. They report a case of hyperpyrexia in a patient receiving psychotropic agents during a summer heat wave; massive muscle destruction (rhabdomyolysis) with myoglobinuria and acute renal failure make this case of particular interest. Causative mechanisms, preventive measures, and the benefits of prompt recognition and treatment of this condition are discussed.

Although laboratory tests are useful in some cases, the authors question the value of routine blood studies for every patient who takes psychotropic medication. They report results of a questionnaire distributed to all members of their local psychiatric society concerning usual practice among psychiatrists in regard to laboratory tests. Summarizing the arguments for and against routine laboratory studies for all outpatients, they conclude that routine studies provide little useful information.

The authors describe a case of combined lithium and haloperidol toxicity characterized by hyperpyrexia, severe rigidity, mutism, and development of irreversible tardive dyskinesia. This case is similar to four other cases described in the literature and to the neuroleptic malignant syndrome. The authors postulate that two types of combined lithium-neuroleptic toxicity occur: a neuroleptic malignant extrapyramidal syndrome and a lithium toxicity that occurs in combination with phenothiazines, primarily thioridazine. Possible mechanisms and preventive measures are discussed.

The authors report the usefulness of RBC lithium determinations in managing the treatment of tardive dyskinesia. They present a case report in which manic manifestations and tardive dyskinesia symptoms paralleled the rise and fall of RBC lithium and plasma lithium levels were constant during the period of symptom improvement. They conclude that RBC lithium levels appeared to reflect toxicity, control of mania, and symptom suppression of tardive dyskinesia better than plasma lithium levels alone.

The author reviews six topics relevant to the drug treatment of schizophrenia. The quantitative effectiveness of promazine is of interest with respect to the structural models of the phenothiazines and the dopamine theory of schizophrenia. The quantitative effectiveness of antipsychotic drugs is also important in evaluating new agents and therefore relevant to a discussion of two newly released neuroleptics, molindone and loxapine. The author's discussion of high-dose treatment of typical acute schizophrenics or treatment-resistant patients reviews the available data and calls attention to the fact that these areas of pharmacologic research have not received sufficient attention.

1. Pacatal is capable of eliciting therapeutic responses in chronically psychotic patients. 2. It is most efficacious for those aspects of behavior which are related to increased anxiety and least efficacious for judgment, insight, orientation, memory and affect. 3. The clinically significant side-effects are those related to the atropine-like action of Pacatal. Untreated eye complications, following prolonged administration of Pacatal, may lead to ulceration of the corneal epithelium. 4. It is recommended that any prolonged ocular disturbance as a result of Pacatal medication be treated with Neostigmine. 5. All the side-effects produced by Pacatal can be obliterated by symptomatic medication, lowering of daily dosage or discontinuation of the medication. 6. The results obtained with Pacatal are encouraging and warrant further investigation upon a prognostically better group of psychotic patients.

Five patients diagnosed as schizophrenic 15 to 30 years ago by the authors have been treated intermittently since then for frequent periodic attacks. Each patient has undergone marked improvement. On maintenance medication there are very few (usually two to 14) days of illness each year. The most striking change is that their symptoms are now primarily affective in character rather than schizophrenic.

Chiorpromazine, while a drug of proven efficacy in clinical psychiatry, does nonetheless, “backfire” on occasions. Rather than reducing a patient’s anxiety or producing a calming effect, the patients may exhibit increased agitation, paranoid reactions, or heightened anxiety after its administration. This variability of response has been attributed by both clinicians and researchers to differences in the personality structure of the drug recipient. In one of our early studies( 1), we had examined the effects of a number of drugs in normal male volunteers. Clear patterns of action emerged for each drug, but considerable variability of response to each was also noted. In a post hoc analysis of data, we found that our student volunteers could be separated into two contrasting personality types. The first group, which we called Type A’s, were extroverted athletes with a low anxiety level, while the other group, Type B’s, were introverted intellectuals with a high anxiety level. Members of each type showed a distinctly different response to reserpine, phenyltoloxamine, and a placebo. From an examination of the psychodynamics of the two personality types, we inferred that a major factor underlying the variability of response to phenyltoloxamine was the differential meaning that the subjects ascribed to its sedative-hypnotic actions. The subjects in turn reacted differently depending on the meaning of the sedative-hypnotic effects to them. Recently we investigated the psychophysiologic effects of a number of pheno

Because of its close clinical similarity to acute paranoid schizophrenia, amphetamine psychosis may serve as a useful experimental model for schizophrenia. Molecular and clinical studies suggest that both the schizophrenia-like symptoms of amphetamine psychosis and the specific ability of phenothiazines to relieve the symptoms of schizophrenia and amphetamine psychosis may be the result of interactions with dopamine systems in the brain. The author discusses some implications of the roles dopamine and norepinephrine may play in mediating some schizophrenic symptoms.

While the depression that follows a psychotic episode in a late adolescent may be very painful to the patient, the therapist should view it as a good prognostic sign: the patient recognizes his psychic "bankruptcy" and is willing to do some needed therapeutic work. An intensive psychotherapeutic involvement at this crucial time may prevent a later intractable psychosis.

Six hundred forty newly-admitted schizophrenic men in 35 VA hospitals were randomly assigned to chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine and phenobarbital groups. Treatment followed a double blind procedure for 12 weeks. Patients were started on low "equivalent" doses of each drug which were gradually increased in a predetermined manner during the first 4 weeks. During the final 8 weeks, each prescribing physician adjusted the dose for each of his patients in order to evoke an optimal therapeutic response. Average daily doses during the flexible period were: chlorpromazine, 635 mg.; triflupromazine, 175 mg.; mepazine, 190 mg. ; prochlorperazine, 90 mg. ; and perphenazine, 50 mg. Clinical evaluations using two rating scales provided 24 criteria of change. For each criterion, the mean of each of the 6 treatment groups adjusted for the net effect of 12 control variables was compared by analysis of multiple covariance with the mean of every other treatment group at each of thr...

Since 1959 a growing number of reports have described a new type of neurological disorder in mental patients. This disorder, known as tardive dyskinesia, has been observed in approximately 500 cases but, judging from the accurate observations made by three separate groups of investigators, the syndrome is likely to be more frequent than one may suspect. Although manifestations of tardive dyskinesia occur in a number of diseases of the central nervous system, there is considerable evidence that the largescale use of phenothiazines or similar drugs in recent years is responsible for the great number of patients in mental hospitals exhibiting myoclonia and choreo-athetoid symptoms.

The authors discuss a current NIMH program whose purpose is to study the empirical knowledge of senior psychotherapists who treat schizophrenic patients and to translate this knowledge into potential research data. Such data, it is hoped, may add a new dimension to the treatment of the schizophrenic patient, which currently emphasizes the use of drugs. Thus far, the five groups of therapists who comprise the program have agreed upon a working definition of schizophrenia, the qualities of patients and therapists who do well in therapy, and the task of the initial treatment phase.

A study of the effects of discontinuing or reducing maintenance medication in chronic schizophrenic men provided an opportunity to evaluate the clinical usefulness of one of the rapid semi-quantitative urine tests (FPN). The rate of excretion of chlorpromazine and thioridazine after placebos had been substituted was determined and the effects of intermittent administration of drugs were observed. The FPN test performed as expected, also providing some interesting information about patients' drug taking behavior. The lower colorimetric readings obtained with thioridazine were most interesting but do not preclude the use of the test done with strict attention to detail in a clinical setting. As the FPN test is a qualitative procedure, its semi-quantitative potential as used in this study should be considered an approximation yielding usable comparative results.

A longitudinal study was made of 18 young hospitalized schizophrenics who exhibited abnormal movements of a choreiform or athetoid type and 36 schizophrenic controls who were free of movement disorders. The group with movement abnormalities were younger at first hospitalization than the controls and their disease progressed steadily, with early and profound mental deterioration. The majority remained in the hospital for the entire observation period despite intensive treatment efforts, while the control group had shorter hospital stays and showed better treatment response.

Three female schizophrenic patients receiving a combination of psychotropic agents, including the antiparkinsonian agent benztropine mesylate, developed the central anticholinergic syndrome, consisting of hallucinations, anxiety, short-term memory loss, disorientation, and agitation. These symptoms responded dramatically to physostigmine salicylate administered intramuscularly; they were unaffected by placebo injection given on a double-blind basis. In patients receiving multiple psychotropic drugs, evaluation of whether the patient is acting confused because of the combined central anticholinergic properties of these drugs is important. When identified, this syndrome can usually be treated by reduction of the dose of the anticholinergic agents or in special instances by the use of the cholinomimetic agent physostigmine.

Two groups of chronic schizophrenic patients were treated with intensive psychotherapy for a period of two years, starting in 1962 and 1964. Half of the patients also took phenothiazines. Control groups at a local state hospital received phenothiazines but no psychotherapy. A follow-up of the groups on three tests of adjustment, administered at the end of 1967, indicated some trends toward better adjustment by patients who had received psychotherapy but there were no statistically significant differences among the groups.

Various techniques have been tried in an endeavor to control deviant sexual drive. This paper presents the results obtained using a long-acting phenothiazine given intramuscularly and working on a depot basis, the theoretical advantages being a lesser incidence of gynecomastia than with estrogens, and the necessity for less patient cooperation than with oral medication. The results in both sexually normal and deviant groups suggest that the drug is of value in reducing sexual drive and performance, with no undue side effects observed provided antiparkinsonian drugs are given.

During 1964 and 1965 schizophrenic patients treated with phenothiazines as clinic outpatients following hospitalization were studied at six-month intervals by means of a questionnaire. They were compared to a control group of schizophrenics who did not maintain contact with the clinic. The experimental group was rehospitalized significantly less often than the control group, and the decrease in the rate of rehospitalization has continued to the present. The authors believe that adequate and continuing follow-up should be provided for all discharged patients.

The authors report on a year's experience with psychiatric patients from aborigine tribes in West Malaysia. Of the 20 cases seen, all but one were psychotic and 16 were also classified as schizophrenic. Withdrawal and running away were common symptom patterns. Only one patient came from a deep jungle area; the others were from fringe areas where sociocultural disruption was more evident. Because of a good preexisting medical service, these patients were easily managed in a hospital that emphasized their own culture. Follow-up in the jungle or villages by aborigine staff members and the use of long-acting injectable phenothiazines resulted in continued improvement of the patients.

A case of sudden unforeseen death in a young, physically well, acutely catatonic patient has been presented. The findings at necropsy were not sufficient to explain either her death or her psychotic behavior. The terminal period was brief, lasting minutes. Contrastingly, sudden deaths in schizophrenic patients reported in the earlier literature generally were characterized by a terminal period lasting hours or days. The role of phenothiazines in the death of our patient is uncertain. Nonetheless, one should remain alert to the possibility of massive brain-stem inhibition occurring in patients receiving large doses of phenothiazines. The character of our patient's death closely simulates sudden death as described by several authors in physically well adults. These deaths were unrelated to medication and were considered as primarily the result of a physiologic or psychophysiologic hyperreactive state.

To determine whether "phenothiazine death" is a valid entity, the authors examined case studies in the literature for other explanations of these sudden, unexpected, autopsy-negative deaths. The results of their comparisons of a large number of phenothiazine deaths and deaths due to lethal catatonia raise doubts as to the validity of phenothiazine death as an entity.

This collaborative study on the efficacy of high doses of trifluoperazine in chronic schizophrenia showed that treatment response was related to length of hospitalization; short-term patients benefited most. High doses of trifluoperazine were most effective with those short-term patients who had been on a piperazine phenothiazine prior to the study. Also, most placebo patients who had been receiving low doses of phenothiazines before the study did not suffer deleterious effects while they were off medication. Treatment implications are discussed.

The authors report the percentages of patients who failed to adhere minimally to prescribed phenothiazine medication schedules in closed-ward, open-ward, and chronic outpatient treatment situations within a single hospital. An unexpected finding was that significantly more outpatients on thioridazine (55 percent) than on chlorpromazine (15 percent) were not taking minimal amounts of medication. Staff attitudes regarding the usefulness of antipsychotic medications were also studied. The principal factor governing patient intake of medication appeared to be the amount of direct patient supervision.

The authors describe a longitudinal, placebo-controlled study of the response to drug treatment of a 62-year-old schizoaffective patient hospitalized for 40 years. While neither lithium nor a neuroleptic drug alone was effective, both drugs administered simultaneously led to the gradual extinction of a pronounced behavioral cycle and the disappearance of manifest psychosis. The authors suggest a synergistic interaction between the two drugs and stress the need for sustained trials of the combination in patients with similar behavioral cycles.

The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.

This study indicates that Quide is a useful addition to the armamentarium of the physician faced with the difficult problem of treating the chronic hospitalized patient with a schizophrenic illness. Side effects of the drug were generally mild, and there was no evidence that it would produce blood dyscrasias or liver impairment. As a result of the circumscribed nature of this study it would be difficult to determine the long-term effects of the drug. However, the drug has shown no chronic untoward effects in previous studies and no chronic effects from the drug were expected. At the end of the study most of the patients were removed from maintenance doses of the drug. Of the total group one patient was discharged on an indefinite furlough. Another was discharged on a temporary furlough. The remainder of the patients in the study continued in the hospital.

Four patients who developed signs of hepatic and haematological toxicity while being treated with carphenazine hydrochloride are reported. The drug was stopped in one patient and continued in 3. All signs of toxicity disappeared in 12-16 weeks, without any reduction in dosage.

The authors confirm the reports of an Ehrlich-positive mauve-colored spot on chromatograms of urine extracts in certain schizophrenic patients, and a simplified procedure for performing the test is outlined. Although the data are consistent with earlier observations that certain abnormal materials occur with higher incidence in the urine of schizophrenic patients than in nonschizophrenics, experiments using thin layer chromatography of these materials suggest that the abnormal material may be phenothiazine metabolites.

The authors' clinical impression that many depressed patients are admitted to hospitals without having received adequate drug treatment as outpatients was confirmed with a sample of 51 depressed patients. Of these, only 20 percent had received proper drug treatment before referral. The authors propose a larger study of the actual patterns of drug prescription to seek the causes of inadequate treatment.

Because of its subtle symptoms, a diagnosis of akathisia is often overlooked when a patient's symptoms worsen during drug treatment. The symptoms, which include restlessness and anxiety, are much like those of such conditions as tardive dyskinesia, restless legs syndrome, and "molimina crurum nocturna." The author warns that the phenothiazines, thioxanthenes, and butyrophenones exacerbate akathisia and that a careful diagnosis should be made before increasing a patient's medication.

Of 25 chronic schizophrenics in each group on perphenazine and proketazine, 11 patients on each drug showed improvement. The patients with delusions, hallucinations and hyperactivity had the maximal benefit from these psychoinhibiting drugs. Of 25 chronic schizophrenics in each group, 11 improved with nialamide and 7 with MO-482. Seven patients on perphenazine and 8 on proketazine improved either to a moderate or marked degree. Moderate to marked improvement was seen in 3 and 5 patients on nialamide and MO-482 respectively. Apathetic and autistic patients had the maximal benefit from the psychoactivating drugs. These drugs are relatively safe as no serious untoward clinical or laboratory results were observed.

A case of atropine-like poisoning manifested by absence of sweating, hyperthermia, pupillary paralysis, dry mucous membranes, and delirium, is reported. These findings are ascribed to the anticholinergic properties of the tranquilizing agents of the phenothiazine group of drugs.

1. Experience with a new " tranquilizer", Trilafon or perphenazine, in treating 90 chronically psychotic hospitalized female patients for a limited period is described. 2. The effects were noted during the period of active administration of the drug and then for a period after termination of the drug therapy. Seventy-two percent of the patients showed some degree of improvement; 15% rose above minimal clinical gains. 3. Side-effects were not serious, were controllable and no deterrent to therapy. The absence of jaundice, blood-dyscrasia and photo-sensitivity are noteworthy. 4. The overall impression is that Trilafon is a useful drug with possibly distinct advantages over the older " tranquilizers" in the treatment of chronically psychotic hospitalized patients.

The author describes the successful management of two severe cases of tardive dyskinesia with thiopropazate. He concludes that the drug does have a place in the management of tardive dyskinesia even though its mechanism of action and long-range effects are unknown. He cautions, however, that it should be used only in severe cases.

A placebo was abruptly substituted for maintenance antiparkinson drug in 20 patients who had previously shown evidence of a thioperazine-induced extrapyramidal reaction. Within 20 days of this controlled study extrapyramidal reactions reappeared in 16 patients (80%). The recurrence rate of phenothiazine-induced extrapyramidal reactions following withdrawal of maintenance antiparkinson drug will vary with different situations and their incidence can only be determined by clinical trial.

‘Rockland State Hospital, Orangeburg, N. Y. drawn to a form of dance music showing as a chief characteristic a strongly pronounced rhythm which appeared to act on its devotees as a powerful stimulus leading them to the performance of extremely energetic and long-sustained rhythmic movements (Rock ‘n Roll); and this led them to feel that this type of music might be used in an attempt to rouse chronic schizophrenic patients from their apathy and inertia. A series of controlled observations on two groups of 25 chronic schizophrenic patients was undertaken, the second group acting as a control. Each group was subject to two one-hour sessions of rhythmic and non-rhythmic music respectively for a week. Assessments were made of each individual patient by a psychiatrist and a nurse before and after the experiment. The psychiatrist used a io unit scale modified from the scales used by Malamud et al. (i95i). The rating scale applied by the nurse was the Albany Behavioural Rating Scale, Shatin and Freed (1955). The clinical assessments of the rhythmic group showed 9 improved out of 20 and in the rating scale assessments there were 9 improved out of 25. In the non-rhythmic group there were 9 improved out of 25 in the clinical assessments and 8 out of 26 in the rating scale assessments. That is to say that a substantial number of patients in both groups showed appreciable improvement. A sex difference appeared in that the females in the rhythmic group showed a relatively greater improvement than those in the nonrhythmic group.