Persistent Phenothiazine Dyskinesia Treated with Tetrabenazine

Six patients with persistent phenothiazine dyskinesia were treated in a double-blind controlled trial with tetrabenazine 100 mg in divided dosage. In three patients the abnormal movements were abolished and in two others there was some improvement, but this was no greater than that achieved with the diazepam control. Tetrabenazine may be useful in the treatment of some patients with persistent phenothiazine dyskinesia.     

THIORIDAZINE (MELLARIL?) IN PSYCHIATRIC PATIENTS

Thioridazine (Mellaril®) was given to 104 psychiatric patients with a variety of illnesses, chiefly schizophrenic reactions. Of 14 patients treated in a double-blind study with successive one-month courses of drug or placebo, nine improved most on the drug and only one on placebo. These results, although limited, confirm a definite therapeutic action for this compound.Nine of 24 patients were significantly improved after treatment with thioridazine for an average of four months following previous treatwith other phenothiazine tranquilizers. Of ten patients treated intensively with thioridazine after they had not responded to other phenothiazine drugs, two were definitely improved and three were slightly improved. Twenty-eight of 56 patients treated from the outset with thioridazine were significantly improved after an average of six months. Most patients received from 100 to 400 mg. daily. These results were comparable to those obtained from other potent phenothiazine tranquilizers. The drug is particularly advantageous for a group of schizophrenic patients who are sometimes made worse by other phenothiazine derivatives or rauwolfia alkaloids. It should also be suitable for treating patients with psychoneuroses and chronic brain syndromes.Only minimal side reactions were observed, chiefly drowsiness, dizziness and nasal stuffiness. Weight gain occurred frequently during treatment.     

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial.

OBJECTIVE--To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. DESIGN--A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. SETTING--Home care. AIDS services in Lusaka and Ndola. PATIENTS--174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. MAIN OUTCOME MEASURES--Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. RESULTS--The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. CONCLUSIONS--For HIV infected Zambians with diarrhoea of more than three weeks'' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.     

Effect of tetrahydroaminoacridine on cognition,function and behaviour in Alzheimer's disease.

OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer''s disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer''s disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer''s disease and is associated with appreciable toxic effects.     

Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial

Objective To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation.Design Pragmatic randomised controlled trial.Setting National Health Service stop smoking service clinics.Participants 901 people trying to stop smoking.Interventions Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated.Main outcome measures Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke.Results 72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ.Conclusions Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone.Trial registration Current Controlled Trials ISRCTN57852484.     

Healing of gastric ulcers after one,two, and three months of ranitidine.

Ranitidine (150 mg twice daily) was compared with placebo in 42 patients with gastric ulcer. The study was conducted as a double-blind trial for one month, followed by an open assessment of one, two, and three months of ranitidine in the patients with persistent ulceration. Thirty-eight patients completed the double-blind trial. Repeat endoscopy confirmed complete healing in 16 of the 21 who had received ranitidine and five of the 17 who had received placebo (p less than 0.01). The remaining 17 patients with persistent ulceration participated in the open assessment. The combined cumulative healing rates of ranitidine at four, eight, and 12 weeks were 73%, 88%, and 97%. There were no adverse effects or unusual reasons for withdrawal from the study (four patients). Ranitidine appears to be a safe and highly effective treatment of gastric ulceration, with about 90% of ulcers healed after eight weeks.     

Choline in tardive dyskinesia and Huntington's disease.

Eight men, 4 with tardive dyskinesia and 4 with Huntington's disease, were treated with oral doses of choline chloride up to 20 g daily for three to eight weeks. Prior to treatment, 7 of the 8 patients were tested with a graded dose of 3 mg of physostigmine salicylate, a cholinesterase inhibitor. Six of these 7 patients had a favorable acute response to physostigmine. The same six patients had a favorable response to chronic treatment with choline chloride. Relapses following a switch from active treatment to placebo were delayed, but this could not be explained on the basis of the rate of choline disappearance from plasma. Re-treatment with choline chloride reversed relapse in most instances. Choline chloride may ameliorate these movement disorders by increasing central cholinergic activity, but other mechanisms are possible. Its practical importance as a treatment needs further elucidation.     

Sulphasalazine retention enemas in ulcerative colitis: a double-blind trial.

Thirty-four patients with ulcerative colitis completed a double-blind assessment comparing the efficacy of two weeks of treatment with nightly retention enemas containing 3 g sulphasalazine or placebo. Symptom grading, sigmoidoscopic appearance, rectal biopsy specimens, and diary records were used to assess benefit and side effects. The active drug conferred significant benefit compared with placebo as shown by several criteria, but this benefit was confined to patients not already taking sulphasalazine by mouth. Overall assessment showed improvement in 11 of the 16 patients (70%) given the active treatment but in only two of the 18 (11%) given placebo. No side effects attributable to the drug were observed, even in patients previously intolerant to oral preparations. The logical therapeutic role of sulphasalazine enemas in ulcerative colitis would appear to be in patients who experience side effects such as nausea, abdominal discomfort, or headaches when taking the drug by mouth.     

Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical outcome at one year.

A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse. The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared. Fifty four stable, remitted outpatients meeting the American Psychiatric Association''s DSM-III criteria for schizophrenia were randomised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections. Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up. Eight (30%) of the patients given placebo injections and only 2 (7%) of the controls, however, had a recurrence of schizophrenic symptoms. Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia. Dysphoric and neurotic symptoms were identified before eight out of 11 relapses, and these symptoms were more frequent in patients given placebo depot injections. These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill, chronic, stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse.     

Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.

OBJECTIVE--To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. DESIGN--Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. SETTING--Primary care in Oxfordshire. SUBJECTS--91 patients in primary care who had major depression. MAIN OUTCOME MEASURES--Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. RESULTS--At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. CONCLUSIONS--As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.     

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE--To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud''s phenomenon associated with systemic sclerosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Dermatology outpatient clinic. PATIENTS--Twenty three patients with Raynaud''s phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS--Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT--Reduction in number, duration, and severity of attacks of Raynaud''s phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS--Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud''s phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION--Both iloprost and nifedipine are beneficial in the treatment of Raynaud''s phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.     

Effect of transdermally administered hyoscine methobromide on nocturnal acid secretion in patients with duodenal ulcer.

Use of anticholinergic drugs in treatment of duodenal ulcers is limited by the side effects of widespread parasympathetic blockade evoked by usual therapeutic doses. A study was conducted into the effectiveness of transdermal delivery of hyoscine methobromide using a new system which releases the drug into the circulation at a controlled rate. In six patients whose duodenal ulcer had healed secretion of acid was measured over two nights, the first on placebo and the second on hyoscine methobromide. All patients responded to the active drug and showed a significant inhibition of acid secretion. Four subjects complained of a dry mouth after overnight treatment with hyoscine methobromide; no other side effects were reported. Transdermal delivery of anticholinergic drugs may be useful in maintenance treatment of duodenal ulcers and further clinical tests are indicated.     

Simple treatment for chronic female infections

A prospective, double-blind, placebo-controlled crossover study of the use of quinine for nocturnal leg cramps was carried out in 8 elderly volunteer patients. The patients were randomly assigned to receive either placebo or 200 mg of quinine sulfate by mouth at bedtime. After 4 weeks of treatment and after a one-week washout period, the group taking quinine switched to placebo and vice versa for another 4 weeks. The differences in the number, duration, and severity of cramps and the side effects were compared. All of the patients had fewer cramps and decreased severity and duration of attacks while receiving quinine. Mild side effects developed in only 2 patients, and these subsided without treatment or discontinuing the medication. We conclude that quinine was effective in relieving nocturnal leg cramps in a selected group of elderly patients.     

Effects of methyldopa on prolactin and growth hormone.

The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal.     

Anabolic steroids in athelics: crossover double-blind trial on weightlifters.

Thirteen experienced male weightlifters taking high-protein diets and regular exercise took part in a double-blind crossover trial of methandienone 10 or 25 mg/day to seeif the drug improved athletic performance. Their improvemments were significantly greater on methandienone than on placebo; their body weights rose (though this seemed to be associated with water retention); and systolic blood pressure rose significantly. Methandienone caused many side effects, and three men had to withdraw because of them. All side effects disappeared after the drug was stopped. Anabolic steroids are effective only when given combination with exercise and high-protein diet.We deprecate their use in athletics but can suggest no way of stopping it.     

Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria.

STUDY OBJECTIVE--To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy. DESIGN--Randomised follow up study of normotensive diabetics with persistent microalbuminuria (30-300 mg/24 hours) treated with enalapril or its matched placebo for one year. Double blind for first six months, single blind for last six months. SETTING--Diabetic clinic in tertiary referral centre. PATIENTS--Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria. INTERVENTIONS--Treatment group was given enalapril 20 mg daily and controls matched placebo. Patients were given antihypertensive treatment after one year. END POINT--Albumin excretion, arterial pressure, and renal function. MAIN RESULTS--In last three months of trial three of 10 patients taking placebo had diabetic nephropathy (albumin excretion greater than 300 mg/24 hours). No patients taking enalapril developed nephropathy and five showed normal albumin excretion (less than 30 mg/24 hours) (p = 0.005, Mann-Whitney test). Mean arterial pressure was reduced by enalapril throughout study (p less than 0.005) but increased linearly with placebo (p less than 0.05). Albumin excretion decreased linearly with enalapril but not placebo. An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure (r = 0.709, p less than 0.05, Spearman''s rank test). With enalapril total renal resistances and fractional albumin clearances improved progressively (time effect, p = 0.0001). CONCLUSION--Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria. This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure. Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs.     

Effect of toremifene in breast cancer patients. Preliminary communication

Toremifene, an antiestrogenic drug administered at three dose levels (60, 120, and 300 mg/day) was investigated in 17 postmenopausal patients with advanced breast cancer previously treated with hormonal and/or cytostatic therapy. The drug proved to be well tolerated at all dose levels without any serious side effects even on prolonged administration. Neither response nor side effects have shown any dose dependency in this small group of patients.     

Observations on the Antipruritic Effect of Guanethidine in Atopic Dermatitis

Guanethidine, 0.75 to 1.25 mg. per kg. per day, was found to alleviate the pruritus of acute atopic dermatitis in 19 out of 20 patients. It was not effective in patients with other dermatoses. An apparent partial tolerance to this treatment developed in six out of 10 patients re-treated. It had little or no therapeutic effect in 10 patients with a variety of other pruritic dermatoses, suggesting that this drug has a specific antipruritic action in patients with atopic dermatitis. In a double-blind study, 11 of 12 patients with atopic dermatitis treated with guanethidine experienced relief of pruritus. Four out of 12 patients using a placebo had complete or partial relief. Guanethidine, 1% to 10%, used topically was therapeutically no more effective than placebo. In view of the reported side effects and the anesthetic hazard encountered with guanethidine, further long-term studies are indicated before this drug is adopted for clinical use in the treatment of atopic dermatitis. The findings support the hypothesis that atopic dermatitis may be a manifestation of a hereditary defect in cutaneous noradrenaline binding.     

Course of patients discharged early after myocardial infarction.

Two hundred and seventy-one (76%) out of 358 survivors of infarction were discharged by the eighth hospital day, and 251 (93%) of them survived to six weeks after discharge. Six of the 20 patients who died between discharge and six weeks did so after readmission and 14 died as outpatients. All these patients who died at home had transmural infarction and four had diabetes. In inpatients successful resuscitation occurred mainly within the first 48 hours, with only three successful long-term results from all the patients who suffered arrest later. This suggests that more prolonged inpatient care would not have reduced the late mortality. These figures justify continuing with an early discharge policy for most patients, but coronary care should probably be more prolonged for patients with diabetes.