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Double-blind study of imipramine and placebo for incontinence due to bladder instability.

We compared imipramine with placebo in a double-blind study in Leicester, in elderly incontinent patients. The results revealed that 14 out of 19 patients became dry after imipramine and six out of 14 after placebo treatment. Patients on imipramine also tended to become drier sooner. However, these results must only be taken as preliminary evidence of drug effect since statistical analysis between drug and placebo did not reach significance. The results do, however, confirm the great benefit of habit-retraining which all patients received. It is now our practice to try this alone first, and to reserve drugs for slow or nonresponders, because of their possible adverse effects.

Aged↗

Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies.

BACKGROUND: S-Adenosyl-L-methionine (SAMe), a natural compound, is the most important methyl donor in the central nervous system. In several clinical trials, SAMe showed antidepressant activity. OBJECTIVE: Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18] to confirm the efficacy and safety of SAMe in the treatment of major depression. In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies, the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design. DESIGN: In MC3, 143 patients received oral SAMe and 138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk. In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint. Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders, responders being those patients showing a decrease in HAM-D score of >or=50% from baseline. RESULTS: In both studies, the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure. However, significantly fewer adverse events were observed in the patients treated with SAMe. CONCLUSIONS: The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally, but SAMe is significantly better tolerated.

Adult↗

Effects on sleep: a double-blind study comparing trimipramine to imipramine in depressed insomniac patients.

Trimipramine, a sedating tricyclic antidepressant, and imipramine were compared on polysomnographic parameters during a 4-week double-blind trial in depressed patients with insomnia and anxiety. Trimipramine eliminated objective evidence of sleep disturbance. This was not the case with imipramine, although depression improved similarly in both groups. Subjects' sleep appeared unchanged or more disturbed at the end of the treatment with imipramine. For trimipramine, the major changes in sleep parameters occurred during the first week of drug administration and did not parallel the gradual changes seen in the measures of depression. Additionally, trimipramine did not suppress REM sleep even in a subgroup of six trimipramine patients who had short rapid-eye-movement (REM) sleep latencies during the placebo baseline period, even though their depression was alleviated. The data demonstrate that (a) antidepressants may vary in their effects on sleep, even though they have similar effects on depression; (b) REM sleep suppression does not necessarily accompany improvement in depression; and (c) reports of improved sleep by patients undergoing antidepressant therapy may not reflect improvement on objective measures of sleep. The different sleep effects suggest the possibility of different antidepressant pathways.

Adolescent↗

A pilot controlled study of the use of imipramine to reduce myotonia.

It has been hypothesized that myotonic dystrophy is caused by a generalized disorder of membrane aminergic and petidergic receptors. A single uncontrolled study has suggested that the affective symptomatology and muscular disability of this disorder might be improved by tricyclic antidepressant treatment. In the present study, 12 adult patients with myotonic dystrophy (age range 18-55 yr) were treated with imipramine and placebo in a double-blind crossover paradigm. Both grip and percussion myotonia were significantly improved by imipramine treatment independent of change in depressive symptomatology. Serum drug levels revealed nonlinear elimination kinetics for imipramine in this patient population.

Adult↗

Plasma beta-endorphin is not affected by treatment with imipramine or paroxetine in patients with diabetic neuropathy symptoms.

To determine the possible role of endogenous opioid peptides in the action of imipramine and paroxetine in painful diabetic neuropathy, beta-endorphin concentrations in plasma were measured in 20 patients during a double-blind, placebo-controlled randomized three-way crossover trial. Despite a significant reduction in neuropathy symptoms during both imipramine and paroxetine treatment, the beta-endorphin level was unaltered throughout the study. The plasma concentration of beta-endorphin was not related to plasma drug concentrations. Thus, this study does not provide evidence of a role of endogenous opioid peptides in the mechanism of action of imipramine and paroxetine in painful diabetic neuropathy.

Adult↗

Platelet imipramine binding in depressed children and adolescents.

Kinetic constants of platelet imipramine binding were determined in youths with major depression, and a contrast group. Subjects actively depressed (N = 10) had significantly fewer imipramine binding sites (Bmax) (877 +/- 148 fmol/mg protein) than recovering depressives (N = 12) (1220 +/- 428 fmol/mg protein) and contrasts (N = 10) (1270 +/- 230 fmol/mg protein). Affinity constants (Kd) (1.14 +/- 0.36 nM, 0.97 +/- 0.31 nM, and 1.17 +/- 0.39 nM, respectively) were similar among the groups. Actively depressed males but not females had fewer imipramine binding sites than both their sex-matched comparison groups. Although actively depressed females' Bmax was significantly lower than recovering depressed and nondepressed males, neither age, Tannner stage, nor circannual rhythms influenced Bmax, but suicidality may be associated with low Bmax. A decrease in Bmax may be a state-specific marker of major depression in boys or associated with a depressive disorder with a suicidal history.

Adolescent↗

A controlled study of trazodone, imipramine, and placebo in outpatients with endogenous depression.

A 4-wk double-blind controlled study of the antidepressant efficacy of the triazolopyridine derivative trazodone, in contrast to imipramine and placebo, was carried out in 30 endogenously depressed outpatients. Trazodone was found to be equivalent in efficacy to imipramine and statistically significantly superior to placebo. Trazodone showed a significant antidepressant effect relative to placebo when outcome was measured after only 7 days of treatment. This antidepressant effect was sustained for at least 5 mo as indicated by an open study phase following the double-bind study. Side effects, particularly anticholinergic properties, were significantly less apparent on trazodone compared to imipramine. A limited study of the relationship of trazodone plasma levels to therapeutic outcome revealed no simple linear relationship and represents a direction for future research.

Adult↗

The side effects burden of extended imipramine treatment of panic disorder.

In a recent study, the authors gauged the net effectiveness of imipramine to be 53%; that is, of 110 patients having panic disorder with agoraphobia who started a course of imipramine at a fixed, targeted, weight-adjusted dose of 2.25 mg x kg(-1) x day(-1), 59 adhered to the regimen and showed a marked and stable response. The present study investigated in detail the side effects burden of imipramine treatment in the same sample using hierarchical linear modeling in a short-term perspective, based on data at baseline (N = 110) and at weeks 1, 2, 4, 6, and 8 (N = 77) of treatment, and a long-term perspective, based on data at baseline and at weeks 8, 16 (N = 66), and 24 (N = 59). Deviations from the general pattern were explored by considering only severe side effects or only completers of treatment to better gauge the clinical significance of the findings. The results revealed that of 15 complaints systematically elicited using a side effects inventory, only 3--dry mouth, sweating, and constipation--continued as a substantial burden at the end of 6 months of treatment. On most other items, the initial increase was followed by a decrease to lower than baseline at the end of treatment. In the case of nausea, vomiting, increased energy, headache, and sexual disorders, the complaints were at their worst before treatment started and improved over the course of treatment. A sustained heart rate elevation between 10 and 15 beats per minute was found, but there were no significant effects on blood pressure or weight. The discussion underscores the need for more methodologically improved comparative studies with selective serotonin reuptake inhibitors in the treatment of panic disorder.

Adult↗

A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression.

Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.

Adolescent↗

A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder.

This was a 6-week, double-blind comparison of fluoxetine, imipramine, and placebo in 89 patients with bipolar depression. Using the criteria of greater than or equal to 50% improvement in the HAMD-total score after at least 3 weeks on study drug, endpoint analysis showed 86% of the fluoxetine-treated patients improved compared with 57% of the imipramine-treated and 38% of the placebo-treated patients. Significantly fewer fluoxetine-treated patients discontinued due to adverse events than did imipramine-treated patients (7% vs. 30%, respectively).

Adolescent↗

A multicentre comparative trial of moclobemide, imipramine and placebo in major depressive disorder. UK Moclobemide Study Group.

The reversible, selective monoamine oxidase A inhibitor moclobemide (450 mg daily) was compared with imipramine (150 mg daily) and placebo in a multicentre, controlled clinical trial lasting 6 weeks. Two hundred and forty-nine patients participated, with a major depressive episode according to DSM-III criteria, and whose initial Hamilton Depression Scale rating (HDRS) was at least 17. Clinical improvement, as determined by HDRS, was similar in the three treatment groups: 53% of the evaluable patients in the moclobemide group responded (i.e. a 50% reduction in HDRS), compared with 50% on imipramine and 51% on placebo. Tolerability was least on imipramine, largely due to the high frequency of anticholinergic side effects; moclobemide showed no difference from placebo in this respect.

Adolescent↗

Initial depression and response to imipramine in agoraphobia.

Thirty-seven patients participating in a controlled treatment study with imipramine were classified as high or low depressed simultaneously on two depression measures. Analysis of variance by 2 (high-low depressed) X 2 (high-low imipramine dosage) groupings revealed significant dose but no depression main effects. The greater dose effect observed in the low depressed group and the greater response rates found among high-dose patients with low initial depression strongly suggest that the beneficial effect of imipramine in agoraphobia was not primarily antidepressant in nature.

Agoraphobia↗

Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine.

Sixty male veterans with posttraumatic stress disorder (PTSD) participated in an 8-week, randomized trial comparing phenelzine (N = 19), imipramine (N = 23), and placebo (N = 18). Mean treatment retention was better on phenelzine (7.4 weeks) than on imipramine (5.6 weeks) or placebo (5.5 weeks). By week 5, both medications significantly reduced PTSD symptoms, as assessed by the Impact of Events Scale (IES), but the 44% improvement on phenelzine was greater than the 25% improvement on imipramine. The intrusion, but not the avoidance, subscale of the IES showed significant improvement, and the initial mild to moderate depressive symptoms did not significantly improve.

Adult↗

Immunoassay reagents for psychoactive drugs. Part 5. Quantitative determination of imipramine and desipramine by fluorescence polarization immunoassay.

Two methods for the quantitative determination of imipramine (IMI) and desipramine (DMI) by fluorescence polarization immunoassay (FPIA) are described. One immunoassay allows for the accurate quantification of imipramine in the presence of desipramine, while the other allows for the accurate quantification of desipramine in the presence of imipramine.

Chromatography, High Pressure Liquid↗

Thioridazine interferences with imipramine metabolism and measurement.

A case is presented in which toxic concentrations of imipramine (Tofranil) resulted from the co-administration of low-dose thioridazine (Mellaril). This probably occurred in an individual with genetically reduced capacity for oxidative drug metabolism, specifically via thioridazine's interference with the hepatic cytochrome P450IID6 isoenzyme (CYP2D6). In addition, coelution of thioridazine and its metabolites resulted in false elevations of imipramine and desipramine as measured by a common high-performance liquid chromatography (HPLC) method (cyanopropyl column). In contrast, an enzyme immunoassay (Abbott TDxFLx) and a second reference HPLC method (silica column) accurately resolved the analytes. This combination of psychiatric drugs is not uncommon in the pediatric population and is one of which both clinicians and laboratorians need to be aware. To the author's knowledge, this is the first report of interferences of thioridazine with both the metabolism and measurement of imipramine in a pediatric patient.

Antidepressive Agents, Tricyclic↗

Dopamine D3 receptor antisense oligodeoxynucleotide potentiates imipramine-induced dopaminergic behavioural supersensitivity.

Chronic antidepressant treatments result in the potentiation of dopaminergic transmission in the mesolimbic dopamine system revealed as an increased motor response to dopamine D2-like agonists. On the basis of the involvement of this system in the control of motivation and reward-related behaviour, which are impaired in depression, it has been suggested that such supersensitivity might play an important role in the mechanism of action of these drugs. Several studies have provided evidence suggesting a role of dopamine D3 receptors in mediating antidepressant-induced increased motor response to dopamine agonists. To test this hypothesis, we studied the effect of the intracerebroventricular infusion of a dopamine D3 receptor antisense oligodeoxynucleotide (10 microg/3 microl, 2-3 daily injections) on the expression of imipramine-induced supersensitivity (20 mg/kg daily intraperitoneal injections for 21 days) to the motor effect of the dopamine D2-like receptor agonist quinpirole (a single 0.3 mg/kg subcutaneous injection 24-48 h after imipramine withdrawal). The results show that a treatment previously shown to reduce the synthesis of dopamine D3 receptors, rather than resulting in an inhibitory effect, potentiated the ability of imipramine to induce dopaminergic motor supersensitivity. The present results suggest that increased dopamine D3 receptor expression following antidepressant treatments is not involved in the mechanism of dopaminergic supersensitivity, and are consistent with evidence supporting an inhibitory role for dopamine D3 receptors in motor activity, both in normal and in sensitized subjects.

Animals↗

Imipramine and buspirone in patients with panic disorder who are discontinuing long-term benzodiazepine therapy.

Pretreatment with imipramine, buspirone, or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use. The average duration of benzodiazepine use was 75 +/- 64 months, and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 +/- 19 mg/d. We hypothesized that pretreatment with either imipramine or buspirone, in contrast to pretreatment with placebo, would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines, thus making the taper process easier to complete. All 3 treatments (imipramine, buspirone, and placebo) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups.

Adult↗

African women with depression: the effect of imipramine and fluoxetine on body mass index and leptin secretion.

Treatment of depression is often accompanied by weight changes. Previous studies indicate that leptin plays no role in this change despite showing a strong correlation with body mass index (BMI) in healthy people. The aim of this study was to evaluate the effect of imipramine and fluoxetine on BMI and its correlation with leptin. Eighteen depressed female patients randomly received either drug for 3 months. BMI was calculated and fasting blood samples were assayed for glucose, leptin, insulin, free fatty acids (FFA), and lipids. The difference between the changes in BMI (imipramine + 1.0 kg/m2, fluoxetine -0.5 kg/m2) was statistically significant (P < 0.05, t = 2.106). There was a significant positive correlation between overall BMI and leptin (r = 0.784, P < 0.001) but not between BMI and insulin or FFA. However, fasting insulin levels and calculated insulin resistance levels dropped substantially in the imipramine group. We conclude that the use of tricyclic antidepressants (TCAs) in depressed patients at risk for developing type 2 diabetes remains unresolved at this stage.

Adult↗