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PubMed1992

Imipramine induced heart failure in the dog: a model to study the effect of cardiac assist devices.

OBJECTIVE: The value of intravenous imipramine in creating a reversible model of short term heart failure was evaluated in anaesthetised dogs. METHODS: Acute effects of imipramine were studied in 11 dogs using invasive haemodynamic pressure measurements and two dimensional echo evaluation. RESULTS: After a 30 min imipramine infusion (7.5 mg.kg-1.h-1), positive left ventricular dP/dtmax decreased from 1368(SEM 108) to 909(119) mm Hg.s-1 (p < 0.05), left ventricular end diastolic pressure increased from 8(1) to 12(2) mm Hg (p < 0.05), while left ventricular pressure decreased from 106(4) to 87(6) mm Hg (p < 0.05). Cessation of imipramine administration resulted within 60 min in partial restoration of cardiac function. This deterioration and subsequent recovery was also demonstrated with echocardiographic measurements, which showed a decrease in ejection fraction from 54(3)% to 28(2)% (p < 0.05). During administration of imipramine neither significant electrophysiological changes nor supraventricular/ventricular arrhythmias were seen. Repeated infusions of imipramine in three anaesthetised dogs with a two week interval showed the reproducibility of the haemodynamic effects and the recovery of ventricular function. Since the model was developed to evaluate the use of cardiomyoplasty in heart failure, the effect of imipramine was also evaluated on latissimus dorsi muscle contraction. Administration of imipramine did not affect skeletal muscle force development at the dosage used to create heart failure. CONCLUSIONS: This model can be used to produce short term reversible heart failure in anaesthetised animals to test the efficacy of supportive interventions like dynamic cardiomyoplasty, intra-aortic balloon pumping, and mechanical cardiac assist devices.

Animals↗
PubMed1996

Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients.

The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder.

Adult↗
PubMed1996

Steady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4'-hydroxylation status in Japanese depressive patients.

The steady-state plasma concentrations of imipramine and desipramine were measured after a more than 2-week treatment with 0.39 to 1.39 mg/kg/day of imipramine hydrochloride in 28 Japanese patients with major depression who had been phenotyped simultaneously with mephenytoin (for CYP2C19-related status) and with metoprolol (for CYP2D6-related status) before initiating the antidepressant therapy. Patients consisted of five poor metabolizers (PMs) of CYP2C19 with an extensive metabolizer (EM) phenotype of CYP2D6, whereas the remainder were EMs for both of the phenotypes. The mean respective concentrations (corrected by mg/kg) of imipramine and the sum of imipramine plus desipramine were 2.4 and 1.8 times greater in the CYP2C19-related PM than in the EM group, and these two variables correlated with the log10 urinary excretion of 4'-hydroxymephenytoin (rs = -0.73 and -0.64, both p < 0.01, respectively), but not with the metabolic ratio (MR) of metoprolol/alpha-hydroxymetoprolol. The mean N-demethylation index (MR of desipramine/imipramine) was significantly (p < 0.01) less in the PM than in the EM group. This index correlated with the 4'-hydroxylation of S-mephenytoin (rs = -0.51, p < 0.01), but not with the alpha-hydroxylation of metoprolol, implying that imipramine N-demethylation is under a coregulatory pharmacogenetic control of CYP2C19, but not of CYP2D6. In conclusion, by taking into account that the incidence of the PMs of CYP2C19 is much greater (18-23%) than that of CYP2D6 (< 1%) in Japanese population, the individually predetermined assessment of the CYP2C19-mediated metabolic capacity of imipramine would be more valuable than that of the CYP2D6-mediated capacity for forecasting the steady-state concentrations of imipramine and desipramine in Japanese depressive patients, thereby attaining an individualized optimization of imipramine therapy. Obviously, a pharmacodynamic assessment study conducted simultaneously with predetermined CYP2C19 status is required for supporting this contention.

Adult↗
PubMed2000

Therapeutic effects of imipramine are counteracted by its metabolite, desipramine, in patients with generalized anxiety disorder.

Imipramine has been shown to reduce anxiety in patients with generalized anxiety disorder (GAD). However, some properties of imipramine may diminish or counteract its anxiolytic effects. The authors previously found that the greater the reduction in cardiac vagal control after 6 weeks of imipramine treatment, the smaller the improvement in anxiety-related symptoms. The purpose of this study was to determine whether the authors' previous findings were replicable and to gather information on the plasma levels of imipramine, desipramine (the major metabolite of imipramine), and anticholinergic levels. Fourteen patients with GAD were administered imipramine for 6 weeks. Their scores from self-administered and investigator-administered rating scales were obtained before and after the treatment, and the changes in these scores were contrasted with the changes in cardiac vagal tone, along with the absolute plasma levels of imipramine, desipramine, and anticholinergic activity at the end of week 6. The authors observed a greater improvement in symptoms of anxiety in those who showed the smallest decreases in cardiac vagal tone and in those who showed the smallest increases in desipramine and anticholinergic plasma levels. Moreover, strong relationships were observed between desipramine and anticholinergic levels. These results demonstrate that imipramine not only has therapeutic effects, but it may also have properties that result in physiologic states that counteract its therapeutic effects. Future research should investigate the direct anticholinergic effects of desipramine and determine whether there is a parallel between the anticholinergic effects and the clinical outcome of other pharmacologic treatments, including antidepressants with predominantly norepinephrine or serotonin reuptake inhibitory properties.

Adrenergic Uptake Inhibitors↗
PubMed2002

Specific side effects of long-term imipramine management of panic disorder.

In a recent study, the authors suggested that tachycardia, dry mouth, and sweating continued to burden patients with panic disorder with agoraphobia who have shown marked and stable response to 6 months of imipramine treatment at the fixed, weight-adjusted dose of 2.25 mg/kg/day. Although sexual dysfunction and weight gain were not a significant burden in that study, they are important problems in long-term treatment with antidepressant drugs. In the present study, in the context of a randomized, double-blind, placebo-controlled, 1-year discontinuation and maintenance study of 53 patients with panic disorder with agoraphobia who respond to imipramine, the authors examine the extent and the specificity of these five side effects of imipramine maintenance using data at pretreatment, at the end of 24 weeks of open imipramine treatment (or month 0 of randomization), and at months 2, 4, 6, 8, 10, and 12 of randomized treatment. Hierarchical linear modeling and repeated measures of analyses of variance in subsamples of completers confirmed that dry mouth, sweating, and increased heart rate constitute a significant and specific enduring burden of imipramine maintenance treatment. The data also revealed that weight gain is a significant and specific side effect of 1-year imipramine maintenance treatment; however, the likelihood of reporting sexual dysfunction decreased over time, with no difference between the placebo and imipramine maintenance conditions. The results are discussed in the context of previous studies of imipramine side effects in the management of depression and the available literature of sexual and weight side effects of antidepressant medications in the treatment of anxiety disorders.

Adult↗
PubMed2002

Duration of imipramine therapy and relapse in panic disorder with agoraphobia.

It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse. This study further explores the relationship between relapse and duration of imipramine treatment in this population.Fifty-one patients, all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and randomized to double-blind maintenance or placebo substitution, discontinued imipramine treatment eventually and were followed over a 12-month risk period: 27 during first year placebo substitution, 7 after 12 months of imipramine maintenance in placebo substitution, and 17 after variable durations of imipramine maintenance in open discontinuation. There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation. Duration of imipramine treatment, the method of discontinuation (open versus placebo substitution), or any of the 9 variables from the demographic, clinical, and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse. The rate of relapse after only 6 months of treatment (10 out of 27, 37%) was identical to the rate of relapse after 12 to 30 months of treatment (9 out of 24, 37.5%). The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients. Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction.

Adult↗
PubMed1987

Temperature dependence of drug interaction with the platelet 5-hydroxytryptamine transporter: a clue to the imipramine selectivity paradox.

Although [3H]imipramine is a selective radioligand for the 5-hydroxytryptamine (5-HT) transporter in human platelets, its affinity for binding to the 5-HT transporter complex at 0 degrees C (0.6 nM) is significantly higher than its potency for inhibition of [3H]5-HT uptake at the physiological temperature of 37 degrees C (Ki = 29 nM). As this apparent discrepancy could be related to the assay temperature, we studied the thermodynamics of drug interaction with the 5-HT transporter at assay temperatures between 0 degrees C and 37 degrees C, using as radioligands [3H]imipramine (0 degrees C and 20 degrees C) and [3H]paroxetine (20 degrees C and 37 degrees C), a newly available probe for the 5-HT transporter. At 20 degrees C, Ki values of 14 tricyclic and nontricyclic drugs for inhibition of [3H]imipramine and [3H]paroxetine binding to human platelet membranes were highly significantly correlated (r = 0.98, p less than 0.001), validating the use of these two radioligands to study the 5-HT transporter over a temperature range larger than was previously possible with [3H]imipramine alone. The affinity of imipramine for the 5-HT transporter is progressively enhanced with decreasing incubation temperature, thus favoring the selectivity of [3H]imipramine for the 5-HT transporter at 0 degrees C. At 37 degrees C, the Ki of imipramine for inhibition of [3H]paroxetine binding is 32 nM, and equals its Ki value for inhibition of 5-HT uptake into human platelets. With the exception of chlorimipramine, other tricyclic 5-HT uptake inhibitors showed a temperature sensitivity in their interaction with the 5-HT transporter similar to that of imipramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport, Active↗
PubMed1992

Sodium lactate reversal of electrophysiological effects of imipramine in guinea-pig ventricular myocardium.

Overdose cardiac effects of imipramine are due to fast Na channel blockade and are clinically reversed by administration of sodium lactate which induces alkalosis (about pH 7.50) and hypernatremia (about 8 mM). The mechanisms of this beneficial effect of Na lactate were explored in vitro on guinea-pig ventricular myocardium using the microelectrode technique. The time-course effects of the clinically relevant concentration of 10 microM imipramine on action potential characteristics were examined at pH 7.20 and pH 7.50. To test whether alkalinisation per se is important or whether an increase in Na concentration plays a major role in the reversal effect, preparations were exposed to increasing concentrations (1, 3, 10, 30, 100 mM) of either Na lactate, bicarbonate or chloride in the absence or in the presence of 10 microM imipramine at pH 7.50. The influence of elevating osmolality was evaluated with equivalent concentrations of sucrose. Imipramine alone significantly depressed Vmax and shortened action potential duration at all phases of repolarisation. All three high sodium solutions reversed imipramine effects. However the reversal effect was already obvious with 10 mM Na lactate and 10 mM NaHCO3 but not 10 mM NaCl. Osmolality did not reverse the imipramine-induced Vmax depression. The results suggest that at the clinically relevant 10 mM concentration, sodium lactate and bicarbonate may displace imipramine from its receptor site on the Na channel by causing alkalosis at the membrane level without profoundly affecting the driving force of the Na current, whereas at the upper concentrations, the increase in Na ion concentrations is predominantly involved in the reversal of imipramine effects.

Action Potentials↗
PubMed1990

Double-blind comparison of moclobemide, imipramine and placebo in depressive patients.

In a prospective, randomized double-blind study, moclobemide was compared with imipramine and placebo in the treatment of depressed outpatients. Three parallel groups of 24 patients each received capsules containing 100 mg moclobemide, 33 mg imipramine or placebo for 6 weeks; the maximum daily dose was 6 capsules. The only concomitant psychotropic medication allowed was diazepam for severe agitation or insomnia, and continuation of established lithium prophylaxis; no tyramine restrictions were imposed. Both moclobemide and imipramine were clearly superior to placebo in reducing depressive symptoms, moclobemide showing a somewhat faster response on the Hamilton Rating Scale for Depression than imipramine; the mean final improvement in total score compared with baseline was 48.3% for moclobemide, 50.2% for imipramine and 18.6% for placebo. The difference between moclobemide and imipramine was not significant. Placebo was clearly better tolerated than either active drug, and moclobemide slightly but not significantly better than imipramine. A 52-week assessment in 22 of the patients receiving moclobemide showed that the clinical response was maintained and the long-term treatment was well tolerated. It is concluded that both moclobemide and imipramine were superior to placebo in treatment of major depressive episodes in outpatients. There was a slight tendency to earlier response with moclobemide, probably because it can be given in the full dose from the start of treatment.

Adolescent↗
PubMed1978

The kinetics of imipramine-N-oxide in rats.

Rats were given imipramine-N-oxide as single intramuscular injection and then as repeated oral doses. Imipramine-N-oxide and the metabolites imipramine and desipramine were analysed in the blood cells, plasma and brain tissue. The concentration of imipramine-N-oxide increased simultaneously in the brain and blood, reaching a peak 45 minutes after a single dose. Imipramine was the quantitatively predominant metabolite in the blood cells and brain, while desipramine reached a higher concentration than imipramine in the plasma. Samples taken at different times after oral doses during continuous treatment showed fairly constant concentrations of imipramine-N-oxide and desipramine in the brain, whereas the concentration of imipramine was more fluctuating.

Administration, Oral↗
PubMed1982

Imipramine kinetics in the single pass rat liver perfusion model.

Imipramine elimination and metabolism was studied in a single-pass rat liver perfusion model with flow and pressure kept constant for a perfusion-period of 120-200 min. Imipramine was eliminated from the liver mainly in three ways: unchanged in the outflow medium, by demethylation forming desipramine, and by 2-hydroxylation and subsequent glucuronide coupling. The formed desipramine was eliminated unchanged (outflow) or by 2-hydroxylation + glucuronide coupling. The conjugated metabolites were mainly eliminated via the bile. By perfusion with constant imipramine concentration in the inflow medium (10-15 microM), steady state could not be obtained within 120 min. perfusion time, neither in terms of a constant outflow concentration, nor in terms of balance between input and output. Perfusion with imipramine for 20 min. (single-dose) followed by perfusion with drug-free medium showed an extensive elimination of imipramine (extraction ratio 0.64-0.97) and rapid disappearance of imipramine from outflow medium (t 1/2 5-10 min). A second single dose imipramine perfusion given 70 to 90 min. after start showed a significant reduction in extraction ratio. At the same time the elimination via bile decreased about 50%, and only a fraction of this decrease was accounted for by a decrease in bile flow. The data thus indicate that a gradual decline in elimination rate may explain the difficulties in reaching a steady state during constant infusion with imipramine. Gradual changes in distribution kinetics could not be excluded though. Results of both types of experiments (continuous or single dose administration) indicated dose dependent elimination compatible with saturation kinetics.

Animals↗
PubMed1998

Kinetic interaction between fluoxetine and imipramine as a function of elevated serum alpha-1-acid glycoprotein levels.

The effect of elevated serum alpha-1-acid glycoprotein (AAG) levels on the pharmacokinetic interaction between imipramine and fluoxetine has been examined by utilizing a novel strain of transgenic mice which express serum AAG levels several times greater than normal. Before fluoxetine treatment, serum imipramine levels were approximately three times greater in transgenic mice than in control mice. Despite higher serum imipramine levels in transgenic mice, brain drug levels were lower than those found in control mice. Fluoxetine pre-treatment (20 mg kg(-1) for 5 days) resulted in an increase in serum imipramine levels in both groups of mice and the extent of the increase was greater in transgenic mice than in control mice (4.5-fold increase compared with 3.1-fold). Similarly, fluoxetine pre-treatment resulted in an increase in brain levels of imipramine in both groups of mice and the extent of the increase was greater in transgenic mice than in control mice (3.0-fold increase compared with 2.0-fold). Similar trends were observed for levels of desipramine in the serum and brain. Serum imipramine and desipramine levels did not correlate with their respective brain levels in the presence of elevated serum AAG levels before and after pre-treatment. These findings indicate that the extent of increases in imipramine and desipramine serum and brain levels are greater during elevated serum AAG states than during normal AAG states when imipramine is co-administered with fluoxetine.

Animals↗
PubMed1998

Imipramine decreases oesophageal pain perception in human male volunteers.

BACKGROUND: Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed. AIMS: To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain. METHODS: Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1-3, 50 mg days 4-6, 75 mg days 7-12), with oesophageal perception studied on day 13. RESULTS: Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p = 0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine. CONCLUSION: Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect.

Adult↗
PubMed1997

Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions.

Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with imipramine (20 mg/kg, i.p.) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from several brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 +/- 19.4, imipramine = 154.4 +/- 7.5, P < 0.005) and striatum (control = 850.9 +/- 59.6, imipramine = 742.5 +/- 34.7, P < 0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neurotransmission in the antidepressant effect of imipramine.

Acetylcholinesterase↗
PubMedDate not supplied

Plasma concentration and clinical effect in imipramine treatment of childhood enuresis.

The relationship between steady-state plasma concentraton and clinical effect of imipramine in the treatment of nocturnal enuresis was studied in 22 hospitalised children. After 1 week on placebo the children were given imipramine in a fixed dose of about 1 mg/kg for 3 weeks. The enuresis frequency decreased significantly from the placebo to the first week on imipramine, but then no further improvement was observed. There was a significant correlation between steady-state plasma concentration of desipramine or imipramine + desipramine and the reduction in enuresis frequency during imipramine treatment. The optimum effect was obtained when steady-state levels of imipramine + desipramine were above 60 microgram/L; i.e. the effective concentration in enuresis is 3 to 4 times lower than in antidepressive therapy. Dose- and weight-corrected, steady-state plasma concentration of imipramine and desipramine were not significantly different from those previously observed in younger adults. In 1 child, a transient rise in imipramine and desipramine concentration was seen during a period with fever and bacterial infection.

Adolescent↗
PubMed1993

Fluoxetine compared with imipramine in the treatment of inpatient depression. A multicenter trial.

Fluoxetine and imipramine were compared in a six-week, double-blind, randomized trial in 118 men and women, ages 18 to 70 years, hospitalized for major depressive disorder. Treatment groups were comparable at baseline. Median maintenance doses were: fluoxetine, 80 mg/day; imipramine, 200 mg/day. Efficacy with fluoxetine and imipramine was comparable: none of the between-treatment differences was statistically significant. Mean +/- standard deviation baseline HAMD21 total scores and change (last-visit-carried-forward analysis), respectively, were fluoxetine, 28.0 +/- 5.3 and -8.5 +/- 9.9; imipramine, 27.0 +/- 5.8 and -11.9 +/- 9.0. Response and remission rates, respectively, were fluoxetine, 54.5 and 21.2%; imipramine, 60.0 and 34.3%. Discontinuations for adverse events were comparable (fluoxetine, 21.4%; imipramine, 22.6%). Common treatment-emergent events with fluoxetine were dry mouth (28.6%), constipation (17.9%), and somnolence (17.9%); those with imipramine were dry mouth (58.1%), constipation (32.3%), and headache (22.6%). Fluoxetine was as effective as imipramine in this population of inpatients.

Adolescent↗
PubMed1975

Biotransformation and biliary excretion of imipramine in rats under various experimental conditions.

150 Minutes after intraperitoneal administration of 80 mg 14C-imipramine/kg to male rats, the percentage of the dose found in liver and determined as imipramine plus metabolites is 13-15% independently whether a bile fistula has been inserted or not. 1/4 of this percentage is located in the hepatic microsomal fraction. The simultaneous administration of pentobarbital and/or diphenylhydantoin does not alter these findings. The metabolite pattern, however, is shifted in favor of unmetabolized imipramine. In male rats without bile fistula, the enterohepatic circulation has no effect on the amount and the metabolite pattern of imipramine plus metabolites excreted into bile. In male rats with bile fistula, the biliary excretion of imipramine plus metabolites (87% as conjugated metabolites) over 8 h accounts for 26% of the dose (80 mg imipramine/kg) and follows first order kinetics. In female rats without bile fistula, the percentage of an identical imipramine dose found in liver after 150 min is only 7%. 1/7 of this percentage is located in the hepatic microsomal fraction. The percentage of unmetabolized imipramine in liver is double that found in male rats. Simultaneous administration of imipramine and pentobarbital at the same dosage as in male rats is lethal for female rats without bile fistula within 30 min.

Animals↗
PubMed1989

[A double-blind comparison study of nomifensine and imipramine in treating depressed patients].

Nomifensine was compared to imipramine in treatment of 40 patients with endogenous major depressive disorder. After one week washout, patients were randomly assigned to 5 weeks treatment with Nomifensine or Imipramine. Mean scores for HAM-D, HAM-A, GAS were significantly improved in both treatment groups (P less than 0.01). Two agents were similar in antidepressant efficacy and rapidity of action. Nomifensine treatment group had fewer side effect, whereas the Imipramine group had more adverse experiences. Effects of Nomifensine on the ECG were compared to those of imipramine. Both drugs increased heart rate. Nomifensine less than imipramine. QT measurement interval revealed a statistically significant decrease in imipramine group. Plasma Nomifensine and imipramine concentrations were not correlated with clinical response, side effects or electrocardiographic parameters. The steady-state plasma concentration 105 +/- 47ng/ml for nomifensine, 860 +/- 773ng/ml for imipramine were offaimed respectively at the fixed dose (225mg/day) during the 35 treatment day.

Adolescent↗