Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis was conducted to assess the use of pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitor (SSRI) therapy. METHODS: A comprehensive search of PubMed, Cochrane, Embase, Web of Science, and PsychINFO databases from 1970 through December 2013 was conducted. Only randomized controlled trials (RCTs) studied on unipolar SSRI-resistant depressed adults were included. The primary outcome was mean change scores of depressive symptom on the depression rating scales, assessed with standardized mean differences. RESULTS: Five RCTs consisting of 154 patients met all inclusion and exclusion criteria. The overall pooled effect size in the primary and secondary efficacy analysis showed no significant effects of pindolol plus SSRI therapy (standardized mean difference = -0.43, p = 0.24; OR = 1.92, p = 0.39, respectively). In terms of acceptability, there was no statistical difference in either tolerability or safety between the two groups (OR = 0.46, p = 0.40; OR = 0.90, p = 0.94, respectively). These estimates remained robust through several sensitivity and subgroup analyses, except 7.5 mg-qd pindolol augmentation did show a significant benefit over 2.5-mg tid pindolol augmentation. CONCLUSIONS: Pindolol augmentation may not be suitable for treatment-resistant depression patients with SSRI-resistant depression. However, once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients.

Beta blockers for peripheral arterial disease.

BACKGROUND: Beta (ß) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial because of the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication. This is an update of a review first published in 2008. OBJECTIVES: To quantify the potential harmful effects of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance and skin temperature when used in patients with peripheral arterial disease (PAD). SEARCH METHODS: For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2013, Issue 2). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the role of both selective (ß1) and non-selective (ß1 and ß2) beta blockers compared with placebo. We excluded trials that compared different types of beta blockers. DATA COLLECTION AND ANALYSIS: Primary outcome measures were claudication distance in metres, time to claudication in minutes and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures included calf blood flow (mL/100 mL/min), calf vascular resistance and skin temperature (ºC). MAIN RESULTS: We included six RCTs that fulfilled the above criteria, with a total of 119 participants. The beta blockers studied were atenolol, propranolol, pindolol and metoprolol. All trials were of poor quality with the drugs administered over a short time (10 days to two months). None of the primary outcomes were reported by more than one study. Similarly, secondary outcome measures, with the exception of vascular resistance (as reported by three studies), were reported, each by only one study. Pooling of such results was deemed inappropriate. None of the trials showed a statistically significant worsening effect of beta blockers on time to claudication, claudication distance and maximal walking distance as measured on a treadmill, nor on calf blood flow, calf vascular resistance and skin temperature, when compared with placebo. No reports described adverse events associated with the beta blockers studied. AUTHORS' CONCLUSIONS: Currently, no evidence suggests that beta blockers adversely affect walking distance, calf blood flow, calf vascular resistance and skin temperature in people with intermittent claudication. However, because of the lack of large published trials, beta blockers should be used with caution, if clinically indicated.

[Drug-induced tremor]. / Medikamentös-induzierter Tremor.

Drug-induced tremor is an important differential diagnosis for tremor syndromes. In view of a constantly ageing population and increasingly frequent polypharmacotherapy, identification of potentially tremor-inducing drugs may help generating risk profiles for individual patients. Drug-induced tremor has often been seen as a complication of antipsychotic therapy, but its occurrence has also been described in response to a great diversity of compounds such as antidepressants, sympathomimetics, antiarrhythmics, antiepileptics and other drugs. The present article presents a synopsis of the most prevalent tremor-inducing drugs as well as strategies to overcome drug-induced tremor, either by replacement of the causative drug or by symptomatic therapies.

Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs.

OBJECTIVE: To compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia. ANIMALS: Eight adult mixed breed experimental dogs. STUDY DESIGN: Randomized, controlled trial. METHODS: Dogs received 0.05 mg kg(-1) acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg(-1) intravenously, (IV), parecoxib (1 mg kg(-1) IV), a combination of tramadol 3 mg kg(-1) (IV), parecoxib 1 mg kg(-1) (IV) and pindolol 5 microg kg(-1) (SC), morphine (0.1 mg kg(-1) (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 +/- 0.8 mg kg(-1)) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs' effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in SAS 9.1. RESULTS: Both tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR. CONCLUSION: Tramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.

The use of pindolol with fluoxetine in the treatment of major depression: final results from a double-blind, placebo-controlled trial.

BACKGROUND: Preliminary reports have suggested that concomitant institution of pindolol and serotonin reuptake inhibitors robustly hastens clinical response; however, contradictory evidence from a randomized double-blind, controlled trial was recently reported by this group in a population of depressed patients who were prescribed fluoxetine and pindolol. Herein, we report final results from an extended sample size. METHODS: Drug-free outpatients with a major depressive episode were randomized in a double-blind manner to one of two treatment conditions: fluoxetine (20 mg daily) with pindolol (7.5 to 10 mg daily) or fluoxetine (20 mg daily) with placebo. After 6 weeks, patients were followed for 3 more weeks in a single-blind manner, on fluoxetine and placebo pindolol. RESULTS: Eighty-six patients completed at least 1 or more weeks on protocol, with 45 and 41 patients randomized to the pindolol and placebo groups respectively. After 2 weeks on protocol, partial remission (i.e., at least 50% decrease in depression rating scores from baseline) rates for pindolol (16%) and placebo (19%) groups were comparable. By the study's end, a partial remission was achieved, at least transiently, for 67% of the pindolol group and 80% of the placebo group. Pindolol treatment was associated with statistically significant reduction in blood pressure and pulse as compared to the control group. The two groups did not have overall differences in rates of attrition, time to response, and side effects. CONCLUSIONS: In accord with our previously published findings, these extended results do not support the efficacy of pindolol in hastening clinical response to fluoxetine in a patient population with predominantly chronic and recurrent depression.

Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression.

BACKGROUND: It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features. METHODS: One hundred fifty-five inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique. RESULTS: 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants. CONCLUSIONS: If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.

Cardiac hyper- and hyporesponsiveness after pindolol withdrawal.

Abrupt withdrawal of some beta-adrenergic blockers has resulted in clinical syndromes suggestive of adrenergic hypersensitivity that may be due to an adaptive increase in cardiac beta-receptor responsiveness. it was postulated that the partial agonist activity of pindolol might limit enhanced responsiveness of cardiac beta receptors and prevent or diminish withdrawal manifestations. Pindolol was given to 10 hypertensive patients in doses of 10 mg b.i.d. for at least 4 wk, then abruptly replaced with placebo for 20 days. Cardiac chronotropic responsiveness to isoproterenol was decreased on pindolol and gradually returned to normal over 10 to 20 days with no evidence of enhanced responsiveness. In contrast, both resting and exercise heart rate showed rebound increase in responsiveness between the second to sixth day after pindolol (P less than 0.05). Resting and exercise blood pressures gradually rose to stable values without rebound. Plasma norepinephrine and epinephrine and serum thyroxine and triiodothyronine did not change. These data show that abrupt withdrawal of pindolol after long-term dosing leads to transient cardiac hyperresponsiveness of resting and exercise heart rate at the same time as persistent cardiac hyporesponsiveness to isoproterenol. These opposite effects of pindolol on subsets of cardiac beta-adrenergic chronotropic receptors.

Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low.

OBJECTIVE: Positron emission tomography (PET) was used to examine whether the dose of pindolol used to augment antidepressant medication achieves a significant occupancy of the serotonin type 1A (5-HT(1A)) autoreceptor in depressed patients receiving medication. METHOD: The authors examined eight depressed patients on one of two regimes of pindolol (2.5 mg t.i.d. and 5.0 mg t.i.d.) with PET and [11C]WAY-100635. RESULTS: The 5-mg t.i.d. regime achieved a modest (19%) but significant occupancy of the 5-HT(1A) autoreceptor, while the regime used in the vast majority of clinical trials (2.5 mg t.i.d.) did not achieve a significant occupancy. CONCLUSIONS: The dose of pindolol used in clinical trials is suboptimal and may explain the inconsistent results. Therefore, a thorough test of pindolol's efficacy will necessitate doses higher than those used in present clinical trials.

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension.

Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism).

Variability of response to beta receptor blockade for angina pectoris in clinical trials: a study of pindolol.

In a randomized, controlled study we found a significant decrease in pressure-rate (double) product and an improvement in exercise tolerance in patients with angina pectoris treated with pindolol. However, when patients were observed in a long-term double-blind crossover study, pindolol treatment did not produce a significant improvement in angina pectoris or exercise tolerance over placebo. Patients treated with placebo had a gradual improvement in exercise tolerance, possibly because of the training effect of multiple treadmill tests and increased daily walking. The individual patient response to pindolol varied, with some patients showing clinical improvement and decreased double product with exercise and some having no clinical improvement despite a similar decrease in double product. Angina occurred at a lower double product with exercise, suggesting that beta receptor blockade adversely affected other variables of myocardial oxygen demand or decreased coronary blood supply. This study illustrates the difficulties with patient variability and study design that are encountered in studies of beta blocker agents for angina pectoris.

Pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitors: a double-blind, randomized, controlled trial.

BACKGROUND: Studies of pindolol augmentation of antidepressants in major depressive disorder have produced mixed results, and data in treatment-resistant patients are limited. Here, we report on a double-blind, randomized, controlled 6-week study of pindolol augmentation of selective serotonin reuptake inhibitors (SSRIs) in depressed outpatients resistant to SSRI monotherapy. METHOD: Forty-two outpatients with DSM-IV major depressive disorder who had an insufficient response to an adequate trial of an SSRI (fluoxetine, paroxetine, or sertraline) were randomly assigned to pindolol, 2.5 mg t.i.d., or sham augmentation, in addition to continued SSRI administration. For separate analysis, the control group underwent a single-blinded switch to pindolol, 2.5 mg t.i.d., from week 4 through week 6, while the active group was continued on pindolol augmentation (hemi-crossover design). Change in Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of week 3 was the primary outcome measure. Data were gathered from February 1994 to August 1998. RESULTS: Thirty-eight patients completed at least 1 week on protocol, with 21 and 17 randomly assigned to the pindolol and control groups, respectively. After 3 weeks on protocol, partial response rates (i.e., minimum 50% decrease from baseline in HAM-D score and maximum absolute score of 15) for the pindolol (19% [4/21]) and control (24% [4/17]) groups were comparable. At 3 weeks, the pindolol and control groups demonstrated mean +/- SD decreases in HAM-D scores of 6.5 +/- 9.8 and 9.7 +/- 7.2, respectively. There were no significant differences in antidepressant response or side effects between the 2 groups. CONCLUSION: These results do not support the efficacy of pindolol in augmenting clinical response to SSRIs in treatment-resistant depressed patients.

Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study.

A double-blind, placebo-controlled crossover study was conducted to examine the effects of pindolol for the treatment of 11 patients with impulsive, explosive behaviors and other emotional-behavioral abnormalities as a consequence of brain disease or injury. Pindolol treatment was associated with significant therapeutic benefits without sedation and without the use-limiting side effects that occur with propranolol.

Antihypertensive effect of isradipine on blood pressure at rest and during exercise.

After three months of treatment with isradipine, 20 patients with mild hypertension had reduced their resting blood pressure (BP) from 157/103 to 132/85 mm Hg and their BP during isometric exercise from 192/124 to 166/105 mm Hg. The isradipine dose necessary to normalize BP (both at rest and post-exercise) was 1.25 mg twice daily (2 x 1/2 tablet) in 50% of patients and 2.5 mg twice daily (2 x 1 tablet) in 25%. In the remaining 25% of patients, isradipine was combined with 1 mg/day bopindolol. There were virtually no accompanying side effects; in particular, reflex tachycardia was negligible or absent. It is concluded that isradipine is a reliable antihypertensive treatment in mild-to-moderate hypertension.

Effects on sleep architecture of pindolol, paroxetine and their combination in healthy volunteers.

RATIONALE: The combination of pindolol with a serotonergic antidepressant has been used to speed up the antidepressant response and to augment in cases of resistant depression. Animal studies have suggested that this increased response occurs because of 5HT(1A) antagonist properties of pindolol, which in combination with a serotonergic antidepressant produces a synergistic increase in 5HT in the synapse. OBJECTIVES: To test whether the combination of pindolol with a serotonergic antidepressant produces a synergistic increase in synaptic 5HT by examining the effects on measures of sleep, psychomotor performance and ratings of anxiety. METHODS: Twelve healthy male volunteers took part in randomised crossover study in which they received paroxetine 20 mg/day (or its placebo) for 9 days with a washout period of 5 days between. On day 7 and 9 of each treatment they also received pindolol 2.5 mg (or its placebo) three times a day. Sleep EEG recordings were made on each of the nights on pindolol (or its placebo) and ratings of saccadic eye movement parameters, subjective sleep, anxiety and other adverse events recorded on the following days. Four drug conditions were therefore tested: placebo, pindolol alone, paroxetine alone and paroxetine+pindolol. RESULTS. The combination of paroxetine+pindolol produced an increase in REM suppression and a reduction in SWS compared with other drug combinations. There were no significant effects on the other measures of 5HT function recorded in this study. CONCLUSIONS: REM suppression by the combination was approximately equal to the sum of REM suppression by each drug individually and thus does not show a synergistic effect. However, there was a significant reduction in SWS produced by only the combination treatment, which may suggest a specific effect of the combination on non-REM sleep mechanisms.

EEG effects of buspirone and pindolol: a method of examining 5-HT1A receptor function in humans.

RATIONALE: An involvement of 5-HT(1A) receptors is postulated in the pathophysiology of affective disorders and mechanism of action of antidepressants. Methods for studying their functional integrity in humans are, however, limited. Preliminary data suggests that activation of somatodendritic 5-HT(1A) receptors cause a negative shift in the EEG frequency spectrum. Animal research suggests that pindolol is an agonist at these receptors but an antagonist at postsynaptic 5-HT(1A) receptors. OBJECTIVE: We postulated that while pindolol would antagonise known postsynaptic mediated neuroendocrine responses to the 5-HT(1A) agonist buspirone, both drugs would have a similar effect on the EEG frequency spectrum. METHODS: Fourteen healthy men were administered placebo or pindolol (20 mg orally) 90 min before placebo or buspirone (30 mg orally) in a double blind cross-over study. Plasma prolactin and growth hormone were assayed and EEGs recorded before and after drug administration. RESULTS: A significant negative shift in the EEG frequency spectrum was found for both buspirone and pindolol, with the combination producing a similar effect to each drug alone. In contrast, the neuroendocrine response to buspirone was significantly attenuated by pindolol. CONCLUSIONS: The data obtained are consistent with the EEG effects of buspirone and pindolol being mediated by somatodendritic 5-HT(1A) receptors, in contrast to the neuroendocrine response, which is known to be mediated by postsynaptic receptors. The development of this novel method of assessing somatodendritic 5-HT(1A) receptors in humans is a potentially important advance which may allow the testing of hypotheses of its involvement in depression and response to antidepressants.

Risk of adverse events with the use of augmentation therapy for the treatment of resistant depression.

Augmentation therapy is used for those situations where a patient's depression is either treatment-resistant, or partially and/or insufficiently responsive to treatment. It also may be used to attempt to induce a more rapid treatment response. Using drugs together may increase the risk of adverse effects, through potentiation of existing adverse effects or alterations in plasma concentrations of the drug. It is important that clinicians are aware of potential risks of augmentation therapy. Lithium augmentation of a tricyclic antidepressant is relatively well tolerated and the dangers are no greater than using these medications on their own. There are also no reports of serious adverse events when lithium is added to a monoamine oxidase inhibitor. With lithium augmentation of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) therapy there have been case reports of the development of a central serotonin syndrome, and thus caution must exercised. A serious concern when using a tricyclic antidepressant to augment an SSRI is the effect of the SSRI on the cytochrome P450 system and the resulting significant increase in tricyclic antidepressant blood concentrations. Augmentation with thyroid hormones appears to be well tolerated and effective. Case reports and open studies indicate that augmentation with buspirone and the psychostimulants, carbamazepine and valproic acid (valproate sodium) is effective and results in minimal adverse effects. However, there is no empirical evidence supporting these results. Recent work supports the tolerability and efficacy of pindolol augmentation. Considerable caution should be exercised when combining psychotropic drugs. The practitioner should only do so with a full knowledge of the compounds involved and their pharmacological properties.

Effects of pindolol on serum lipids, apolipoproteins, and lipoproteins in patients with mild to moderate essential hypertension.

The effects of 12 weeks' administration of the beta-blocker pindolol (5 mg twice daily) on serum lipids, apolipoproteins (apo), and lipoproteins were studied in 20 normolipidemic patients with mild to moderate essential hypertension (WHO I-II). Pindolol significantly increased both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), while very-low-density lipoprotein cholesterol (VLDL-C) was significantly decreased. Apo A-II levels were increased significantly and the apo B/apo A-I ratio, which is one of the atherogenic indexes, was decreased significantly after pindolol therapy. Total cholesterol, HDL subfraction cholesterols, the LDL-C/HDL-C ratio, triglycerides, apo A-I, apo B, apo C-II, apo C-III, and apo E did not change significantly.

The use of pindolol in the treatment of essential hypertension: a multi-centre assessment.

A multi-centre general practitioner assessment of pindolol, a beta adrenergic blocking drug, was carried out in 464 patients with essential hypertension. The average daily dose was 21 mg and the average period of observation was 15 weeks. Pindolol was shown to be a safe, effective and well tolerated hypotensive agent. In 227 new cases of hypertension, 148 (65.2%) were controlled on pindolol alone, and in 237 previously treated cases of hypertension 91 (38.4%) were subsequently controlled on pindolol alone. In the remaining cases the addition of a diuretic or other antihypertensive agent was necessary to achieve satisfactory control. The mean blood pressure was lowered from 190/111 mmHg to 154/90 mmHg, a mean fall of 36/21 mmHg. Side-effects were not of a serious nature.

A multi-centre general practice trial of a pindolol/clopamide combination ('Viskaldix') in essential hypertension.

A large, open, multi-centre study was carried out in general practice to evaluate the effectiveness and tolerance of a combination of 10 mg pindolol plus 5 mg clopamide, in single tablet form, in the treatment of patients with essential hypertension. Computer analysis of the records of 8989 patients who completed the 8-weeks' study period showed that treatment with the combination product, in a dosage of 1 tablet daily in 83% of the patients, resulted in excellent blood pressure control in the majority (75%) of cases, irrespective of age or previous antihypertensive treatment, and was particularly effective in those with mild to moderate hypertension who had previously not received any therapy. Side-effects were generally not troublesome and only 8.3% of patients stopped treatment for this reason. The most commonly reported side-effects were dizziness, nausea, tiredness and headache.