Discontinuation Of Drug Treatment Research Articles

Contingent tolerance to carbamazepine is not affected by calcium-channel or NMDA receptor blockers

We previously demonstrated that tolerance to carbamazepine's anticonvulsant effects occurs only with contingent presentation of the drug relative to the seizure (i.e., drug administration before but not after the seizure). Moreover, this tolerance can be reversed by altering the contingencies of drug administration (e.g., giving the drug after the seizure has occured) without discontinuation of drug treatment. These findings imply an associative component to tolerance development in this model. Thus, we evaluated the effects on contingent tolerance development of two agents that have been shown to affect rate of tolerance development and acquisition or retention in other learning paradigms. Rats were electrically kindled in the amygdala until they reliably experienced seizures with each stimuation. In three separate studies, MK-801 (0.3 and 0.15 mg/kg), an NMDA receptor antagonist, and nimodipine (20 mg/kg), an L-type calcium channel blocker, were coadministered with carbamazepine prior to each kindling stimulation to evaluate the rate of tolerance development compared to controls. No effect of either drug was seen on the rate of contingent tolerance development to carbamazepine, suggesting that neither NMDA receptors nor L-type calcium channels are critically involved in this type of tolerance. The contingent tolerance paradigm may, however, prove useful in elucidating novel biochemical mechanisms of associative learning that might ultimately be explored in clinical situations where tolerance is a problem.

Withdrawal of antihypertensive drug treatment: time-course for redevelopment of hypertension and effects upon left ventricular mass.

To examine: (1) in how many treated hypertensive patients it was possible to discontinue drug treatment; (2) the time-course for redevelopment of hypertension after discontinuation of therapy; and (3) whether drug withdrawal was associated with an increase in left ventricular mass (LVM). Fifty-four men with primary hypertension treated for a mean period of 6 years (primarily beta 1-selective beta-blockade) were evaluated for withdrawal of treatment. Exclusion criteria were signs of organ damage, severe hypertension, other serious disease and unwillingness. Treatment was reinstituted if blood pressure increased above a safety level or if symptoms occurred. Echocardiographic estimations of LVM were obtained before withdrawal and 1, 4 and 8 weeks after withdrawal or before return to treatment. Outpatient clinic in a city hospital. A random sample of 56-year-old hypertensive men. Gradual discontinuation of treatment with close follow-up of blood pressure. Number of patients who could withdraw from treatment and who had to return to pharmacological therapy; time-courses for development of hypertension; absolute changes in LVM. Thirty-two patients withdrew from treatment for 1-1000 days. Therapy was reinstituted in all owing to hypertension or symptoms. Serial echocardiograms were obtained in 22 patients. During the drug-free period, relative wall thickness increased, but LVM did not. Patients with rapid redevelopment of hypertension had larger prewithdrawal LVM than patients whose blood pressure increased more slowly. It was possible to withdraw treatment and obtain readable echocardiograms in a minority of the patients. After drug-withdrawal, relative wall thickness increased, but not LVM. We suggest that previously treated patients should be avoided in studies examining reversal of left ventricular hypertrophy.

Characteristics of pharmaceutical opinions written in a Quebec community pharmacy.

To describe the characteristics of pharmaceutical opinions written in a community pharmacy and to estimate the possible effects of these opinions on patient drug profiles. Retrospective survey. The community pharmacy where these opinions were written is located in a rural area of the province of Quebec. Only health-related items are sold and no merchandise is displayed in this pharmacy. Ten pharmacists worked at this pharmacy during the period of the study. Pharmacists were paid when they sent advice to a patient or a physician about the patient's drug profile or about the therapeutic value of a prescribed treatment. This survey included recommendations made from 1978 to 1983. A sample of 600 opinions was drawn at random from a total of 1992 opinions that had been written at the site of the study. The impact of each opinion was assessed by analyzing patient drug profiles for three months after the opinion was written to determine if the recipient had followed the pharmacist's recommendation. Pharmacists, on their own initiative, sent 97.9 percent of the opinions. Only 1.7 percent of the opinions were requested by patients and 0.4 percent by physicians. Most opinions were addressed to patients (86.7 percent) rather than to physicians (13.3 percent). Almost four of five recommendations sent to patients were about compliance (45.1 percent) or were suggestions for improving the therapeutic effect of a medication or replacing a drug with nondrug treatment (33.4 percent). The three most common recommendations sent to prescribers were to replace one drug with another (25 percent), to change the dose or dosing schedule of a drug (16.3 percent), and to discontinue drug treatment (16.3 percent). Chemical stability, underuse or overuse of a medication, and adverse effects were the most frequent causes of recommendations sent to patients. Adverse effects, interactions, and the underuse of a medication were the most frequent reasons for recommendations sent to physicians. The proportion of recommendations that were implemented was 77.7 percent for patients and 58.1 percent for physicians. The pharmaceutical opinion seemed to be a good means of communicating with patients and prescribers on a wide variety of problems encountered in a community pharmacy. It allowed pharmacists to be paid for their expertise even if a drug was not dispensed. Also, the pharmaceutical opinion could compensate for the loss of income when the pharmacist recommended replacing a prescribed medicine with nondrug treatment.

The rights of patients versus the obligations to sponsors in clinical trials

A recent exchange of Letters to the Editor in The Lancet [1,2], has made it evident that the Note for Guidance on Good Clinical Practice for Trials on Medicinal Products in the European Community [3], does not provide sufficient advice on the relation between the patient or volunteer on the one hand and the sponsor and his non-physician executive (e.g. monitors) on the other. Although there is no doubt that the patient's interests as represented by the physician have absolute precedence, the latter's responsibilities are listed after those of the sponsor and monitor. Accordingly, two important rights of the patient, i.e. that of the absolute confidentiality of his history and his clinical data as well as of the right to determine with his physician when to terminate his treatment, are insufficiently dealt with. As has been emphasized by Deutsch et al. [1], the non-physician monitor should, according to the guidelines, assure .. i that informed consent is being obtained and recorded from all patients. Since the signature of the patient is to be proof of his consent, the confidentiality is already broken. He should further check the CRF entries with the source documents, which invariably contain the names of patients at many points, and it is impossible to ensure that all these are blacked out. The Guidelines put the responsibility for discontinuing the trial squarely with the sponsor (2.3 c). The reasons for discontinuance may relate to the subject's safety but they may equally well be organisational or even commercial. There may be occasions where the abrupt discontinuation of drug treatment may be detrimental to the patient or where the change to a replacement medicine may be not without risk to the patient. In diseases in which the drug on trial may be the first efficacious agent to become available (e.g. erythropoietin) a premature termination

(−)-Norpseudoephedrine, but not (±)-amphetamine, prevents the increase in fluid intake associated with ethanol presentation in rats

The effects of daily intraperitoneal administration of ±-amphetamine (AMPH: 4 mg/kg) and (−)-norpseudoephedrine (NPE: 15 or 30 mg/kg) on drinking were evaluated in rats allowed to drink water or a 5% ethanol solution during the 5 h following drug administration. AMPH, but not NPE, significantly increased water intake. Substitution of ethanol for water produced a significant increase in fluid intake in the control group, whereas drinking levels remained unchanged in both AMPH and NPE treated rats. Discontinuation of drug treatment during the regimen of ethanol presentation produced a prompt increase in fluid intake in the NPE, but not AMPH, treated groups. Finally, substitution of water for ethanol led to a significant reduction of fluid intake in all the groups. These results suggest that a light (i.e. NPE), but not a strong (i.e. AMPH) psychomotor stimulant, is able to weaken rewarding properties of diluted ethanol.

Neurophysiologic Studies of Patients with Crohn's Disease on Long-Term Treatment with Metronidazole

Fifty-three patients with Crohn's disease were chosen for this study. They were divided into three groups: the first group (19 patients) was treated with metronidazole and had been receiving the drug for at least 1 year; the second group (13 patients) had previously had the same type of long-term treatment but had been off the drug for at least 3 months before entering the study; the third group (21 patients) had never received treatment with metronidazole. The maximum daily dose of metronidazole used was 800 mg. All patients were examined with a broad set of neurophysiologic investigations devised to reveal signs of peripheral neuropathy. No significant difference was found between the three groups. The conclusion was that a daily dose of metronidazole not exceeding 800 mg is well tolerated by patients with Crohn's disease with regard to objective signs of neurotoxicity. A few patients from all three groups showed a raised perception threshold for changes of temperature in the feet (as compared with the department's normal standard). The results of the test were almost identical in the three groups and thus not connected with the metronidazole treatment. During the study, patients were asked about subjective neurologic symptoms such as tingling and numbness. A few patients from all three groups reported such paresthesias from time to time, but they were of a transient nature, not perpetual, and, in patients taking metronidazole, not aggravated despite continuing treatment with unchanged dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Delta Sleep Ratio

Slow wave sleep abnormalities have long been described in depression but were considered to be nonspecific indicators of psychopathology. Computerized techniques, including amplitude frequency measures and spectral analyses, are permitting new approaches to the examination of delta sleep. Early studies suggested that many depressed patients demonstrate lower delta wave intensity during the first non-rapid eye movement period than the second one. This finding, prominent in middle-aged depressed patients, has led to an examination of the ratio between the first and second non-rapid eye movement periods. This delta sleep measure seems to be a more robust predictor of recurrence than rapid eye movement latency. Analysis of data on 74 patients in a long-term maintenance treatment study for a minimum of 24 months demonstrates that the delta sleep ratio can predict survival time following discontinuation of drug treatment. Individuals with a high delta sleep ratio remain clinically remitted five times longer than those with a low delta sleep ratio.

Zopiclone versus Flurazepam in Insomnia

Zopiclone (7.5 mg), a cyclopyrrolone derivative with a 6.5 h half-life, and flurazepam (30 mg) were compared to placebo in a randomized double-blind study involving 36 adult patients suffering from insomnia. All previous psychotropic drugs were discontinued 1 week prior to the study. During 4 weeks, 12 patients received zopiclone, 12 flurazepam and the others placebo. Thereafter, all patients received single-blind placebo for 3 nights. Rapidity of sleep onset, sleep duration, frequency of nocturnal awakenings, psychomotor coordination and side-effects were assessed daily with a questionnaire and a symptom checklist. The results of the study suggest that zopiclone 7.5 mg was at least as potent as flurazepam 30 mg in inducing and maintaining sleep. Both drugs maintained their efficacy during the 4 weeks of treatment. However, the two drugs differed in that flurazepam impaired psychomotor coordination whereas zopiclone did not demonstrate daytime protracted effects on psychomotor performance. Upon discontinuation of drug treatment, score values of the different sleep parameters under study returned to the baseline values. Side-effects were mild and consistent with earlier studies.

Recent Advances in the Psychopharmacological Treatment of Anxiety Disorders

The authors review recent progress in the pharmacological treatment of anxiety disorders. Most research within the last five years has focused on panic disorder; the findings include support for the usefulness of imipramine and clomipramine and probably other agents; evidence that the benzodiazepines alprazolam, diazepam, lorazepam, and clonazepam are approximately equally effective as antipanic agents; and high variability in relapse rates after discontinuation of drug treatment. Further work is required to determine whether buspirone and other forthcoming serotonin agonist drugs have a role in treating panic disorder and other anxiety disorders. For generalized anxiety disorder, scientific studies do not support the effectiveness of beta blocker; tricyclics may be potentially useful. Psychopharmacological treatments for social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder are also reviewed.

Predisposing Factors for the Development of Malignant Essential Hypertension

To clarify predisposing factors for malignant hypertension, we retrospectively investigated the histories of 39 patients with malignant hypertension and 39 patients with benign hypertension. Between the malignant and benign groups, there was a statistically significant difference in blood pressure but not in age when hypertension was first noticed. The number of patients who had discontinued drug treatment was significantly greater in the malignant group (19; 49%) than in the benign group (11; 28%). Insufficient sleep, overwork, and/or mental burden of long duration were factors noticed within one year before the occurrence of the malignant phase in 11 (37%) of the 30 patients in that group in whom this information was available. Patients in the malignant group tended to belong to a lower social class. These results suggest that severe hypertension from an early phase, interruption of drug treatment, and physical and/or mental burden may predispose to the development of malignant hypertension, and that these predisposing factors are likely to be associated with social class.

Keratopathy in rats after treatment with tilorone.

According to clinical reports, the antitumor drug tilorone induces corneal opacities in patients. The present communication shows that keratopathy can be experimentally reproduced in rats and describes the cellular alterations underlying the corneal opacities. Tilorone was applied either orally (60-90 mg/kg) for several weeks or topically (2%) for a few days. Biomicroscopic examination performed after treatment for 6 weeks or longer revealed fine punctate opacities throughout the corneal stroma. Ultrastructurally, the keratocytes were swollen due to large, optically empty vacuoles in the cytoplasm. Similar, albeit smaller, vacuoles were also numerous in the endothelium and less frequent in the epithelium. Histochemical experiments showed that the cellular alterations represented lysosomal storage of polyanionic substances, most probably sulfated glycosaminoglycans, thus mimicking the cytological picture of mucopolysaccharidosis. Upon discontinuation of drug treatment, the alterations tended not to recede. This keratopathy in rats is part of a generalized mucopolysaccharidosis-like disorder induced by tilorone.

Effects of Nifedipine on Renin Release and Renal Function in Anesthetized Dogs

The effects of nifedipine, classed as a calcium entry blocker, on urinary excretion and renin release were investigated in anesthetized dogs. Nifedipine was infused into one renal artery for three consecutive 10-min periods, at incremental rates of 0.3, 1, and 3 micrograms/min. Intrarenal infusion of nifedipine (3 micrograms/min) produced marked increases in urine flow rate (by 200%) and in urinary sodium (by 210%) and potassium (by 40%) excretion rates of the infused kidney without changes in mean systemic blood pressure, heart rate, glomerular filtration rate, and filtration fraction. Urinary osmolarity was slightly decreased by the drug, but this change was not statistically significant. There were no consistent changes in these parameters for the contralateral noninfused kidney. Renin secretion rate was increased to three times the preinfusion level during infusion of the highest nifedipine dose. The blood flow to the infused kidney was increased, and ipsilateral renal vascular resistance was simultaneously decreased upon nifedipine infusion. These results suggest that a nonhypotensive dose of nifedipine causes an increase in renin secretion and that this drug has a striking effect on the reabsorption of sodium and water by the renal tubules.

Mucopolysaccharidosis-like alterations in cardiac valves of rats treated with tilorone.

The purpose of this study was to examine whether the aortic and mitral valves of rats are involved in the mucopolysaccharidosis-like disorder induced by tilorone. Rats were treated with large doses of the drug for periods of 1-21 weeks. After chronic drug treatment the leaflets of both heart valves were thickened and opaque. In all treated animals the spongiosa layer of the stroma was crowded with vacuolated cells; the fibrosa layer was altered only after prolonged treatment. Ultrastructurally, the vacuolated cells of the spongiosa could be identified as histiocytes and fibroblasts, the former being the most susceptible cell type. The fibroblasts of the fibrosa represented the least sensitive cell type. The histochemical results showed that the clear cytoplasmic vacuoles in the spongiosa cells were due to lysosomal storage of polyanionic material with staining characteristics similar to cartilage matrix. After discontinuation of drug treatment the alterations persisted for several weeks. The present study shows that heart valves are involved in the mucopolysaccharidosis-like disorder induced by tilorone. The molecular pathomechanism of the disorder and the exact identification of the storage material must await further analysis.

Serum prolactin and ovarian function after discontinuation of drug treatment for hyperprolactinaemia: a study with bromocriptine and metergoline.

Serum prolactin (PRL) was estimated for up to 2 months after discontinuation of therapy with either bromocriptine (n = 33; 15 with idiopathic disease, 12 with pituitary microadenoma, and six with macroadenoma) or metergoline (n = 23; 11 with idiopathic disease, and 12 with microadenoma) that had been administered for 8-30 months. Only five patients treated with bromocriptine and two treated with metergoline had PRL levels that remained normal or below 50% of pretreatment values. Among the patients followed-up for up to 12 months, four showed a fall in PRL at 3-4 months, but this was followed by a rise in one patient. Five patients showing persistently lower or normal PRL after drug withdrawal were retested with thyrotrophin-releasing hormone; the two responsive women also had a normal response before treatment. Of 10 patients followed for 9 months, three had persistently normal PRL levels. Amenorrhoea and anovulation recurred, with some delay, in all the patients showing PRL rebound except one. Medical treatment of hyperprolactinaemia only rarely results in permanent benefit.

Tilorone-induced lysosomal storage mimicking the features of mucopolysaccharidosis and of lipidosis in rat liver.

This ultrastructural and histochemical study deals with the lysosomal storage phenomena occurring in the rat liver after repeated oral administration of tilorone, an agent with anti-tumor and anti-viral activities. In the sinusoidal endothelium and in Kupffer cells, the lysosomes were changed into large vacuoles which contained material with the histochemical characteristics of acid glycosaminoglycans. The alterations closely resembled those previously observed in the splenic red pulp of tilorone-treated rats. In hepatocytes, the lysosomes were converted into large multilamellated inclusions indicating storage of polar lipids. The results show that, in the rat liver, tilorone induces cellular alterations mimicking those of inherited mucopolysaccharidoses and lipidoses. After discontinuing drug treatment the two storage phenomena gradually faded at different rates: The lipidosis disappeared within 2 to 4 weeks, whilst mucopolysaccharidosis-like changes were still found 15 weeks after drug withdrawal. The occurrence of lipidosis is not surprising, since by its molecular structure tilorone can be regarded as belonging to the group of amphiphilic cationic drugs which often have this side effect. Much more surprising is the occurrence of mucopolysaccharidosis-like alterations. The exact biochemical identification of the polyanionic storage material and the molecular mechanisms responsible for this drug side effect remain to be established.

Recovery from chlorphentermine-induced phospholipidosis in rat alveolar macrophages: Biochemical and cellular features

Rats were treated for 4 weeks with the amphiphilic, anorexic drug chlorphentermine resulting in the induction of a phospholipid storage disorder in alveolar macrophages. We were interested in studying the effects of the presence of this phospholipidosis on certain biochemical properties of the cells, on the size distribution of the cells, and on the accumulation of macrophages in the lungs. In addition, we examined the temporal profile of return of these characteristics back to normal following termination of drug treatment. We previously reported that the phospholipid content of alveolar macrophages collected by pulmonary lavage was elevated at the end of chlorphentermine treatment, but had returned to the control level by 14 days after drug treatment had ceased (Reasor and Koshut, Toxicol. Appl. harmacol. 55, 334–341, 1980). The macrophages become very heterogeneous in size as a result of drug treatment (Reasor et al., Exp. Mol. Pathol. 31, 297–307, 1979). In the present study, we found that by 14 days of recovery, cells from previously treated rats were indistinguishable in size from controls. We also found that the protein content of the cells and the activities of the lysosomal hydrolases β- N-acetylglucosaminidase and β-galactosidase were elevated as a result of drug treatment and all had returned to the control levels by 14 days of recovery. In contrast, the activity of another lysosomal hydrolase, α-mannosidase, was lower in the cells as a result of drug treatment and did not return to the control level until 28 days of recovery. Nearly three times as many macrophages were lavaged from the lungs of treated animals as controls. Increased numbers of cells were obtained until 35 days of recovery. Therefore, while the phospholipidosis, as measured by cellular content and cell size, was no longer present 14 days after discontinuing drug treatment, certain consequences of the disorder persisted for longer periods of time.

Differential effects of acute and chronic haloperidol treatment on striatal and nigral 3, 4-dihydroxyphenylacetic acid (DOPAC) levels

Chronic treatment of rats with haloperidol (4 weeks, 0.5 or 1 mg/kg) resulted in a significant attenuation of the large DOPAC rise seen in the corpus striatum after acute treatment. This tolerance effect was observed both shortly following termination of chronic treatment and on challenge with a low dose (0.1 mg/kg) of the drug 6–8 days later. In contrast, acute haloperidol treatment resulted in only a small and nonsignificant elevation of DOPAC levels in the substantia nigra, while chronic treatment caused a larger and significant increase in levels of the metabolite. Moreover, the latter effect was also observed in response to haloperidol challenge 6–8 days after discontinuation of drug treatment. The differential pattern of response in these two brain regions is discussed in relation to possible mechanisms mediating striatal tolerance and to recent observations regarding changes in nigral dopamine cell firing after chronic haloperidol treatment.

An analysis of the facilitation of avoidance acquisition produced by d-amphetamine and scopolamine

Albino rats from an inbred strain (F344s) and a random bred Sprague-Dawley derivative (ZMs) were administered intraperitoneal injections of either saline, 1.0 mg/kg d -amphetamine, 0.6 mg/kg scopolamine, or a combination of both drugs (0.5 mg/kg d -amphetamine plus 0.3 mg/kg scopolamine) 30 min prior to daily sessions of 25 trials on a brightness discrimination, active-avoidance task in completely automated Y-mazes. For the ZMs, all drug treatments significantly facilitated acquisition of the avoidance response. This facilitation was due to increase in active responses (incorrect avoidances, intertrial crosses, intertrial motor activity) which provided a behavioral baseline which was compatible with learning the requirements of the task. The major effect of the drugs on the F344s, who normally avoid well, was a disruption of behavior in the Combination group, indicating the importance of assessing the behavioral baseline which exists prior to drug administration. Discontinuation of drug treatment resulted in disruption of avoidance performance which was most pronounced in the ZM rats. In addition, drug termination produced disruption of discrimination performance, providing further evidence that the behavioral decrement was due to dissociation (stimulus change) between the drug and nondrug states.

Selective review of effects of discontinuation of drug treatment: some implications and problems.

The research literature on the effects of discontinuation of drug treatment is reviewed. The implications and problems generated by the increasing body of evidence that the therapeutic effects of ataractic drugs do not transfer to the nondrug state are considered. Effort is also made to elucidate some of the problems which negative effects of drug withdrawal create for drug therapy. Directions are suggested for further research that should lead to increased understanding and knowledge in this area.

PRELIMINARY CLINICAL REPORT

Back to table of contents Previous article Next article ArticleNo AccessPRELIMINARY CLINICAL REPORTCHLORPROMAZINE IN THE TREATMENT OF MENTAL ILLNESS. II: SIDE EFFECTS AND RELAPSE RATESHERMAN C. B. DENBER, and ETTA G. BIRDHERMAN C. B. DENBERSearch for more papers by this author, and ETTA G. BIRDSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.112.6.465AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "PRELIMINARY CLINICAL REPORT ." American Journal of Psychiatry, 112(6), p. 465 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByPsychopharmacology, Vol. 73, No. 4, Vol. 1 / 2Comprehensive Psychiatry, Vol. 11, No. 2British Journal of Psychiatry, Vol. 115, No. 523A Study of the Withdrawal of Chlorpromazine or Trifluoperazine in Chronic SchizophreniaM. R. MORTON1 April 2006 | American Journal of Psychiatry, Vol. 124, No. 11Selective Review of Effects of Discontinuation of Drug Treatment: Some Implications and Problems31 August 2016 | Psychological Reports, Vol. 19, No. 3Psychopharmacologia, Vol. 5, No. 5Journal of Chronic Diseases, Vol. 17, No. 4THE RELATIONSHIP OF CERTAIN ORAL SIGNS IN NEUROPSYCHIATRIC PATIENTS TO DOSAGE OF ATARACTIC DRUGSS. H. BLEICHER, A. I. ISHLER, M. B. PAUL, J. K. KEW, and H. C. RICKARD1 April 2006 | American Journal of Psychiatry, Vol. 118, No. 12A COMPARISON OF URINE PHENOTHIAZINE TEST RESULTS WITH PRESCRIBED MEDICATION DOSAGEFLOYD K. GARETZ1 April 2006 | American Journal of Psychiatry, Vol. 118, No. 12Chlorpromazine in the treatment of mental illness. V: Administrative problemsThe Psychiatric Quarterly, Vol. 32, No. 3Journal of Neurology, Neurosurgery & Psychiatry, Vol. 20, No. 3 Volume 112Issue 6 December 1955Pages 465-465 Metrics PDF download History Published online 1 April 2006 Published in print 1 December 1955