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PubMed1998

Effects of trazodone hydrochloride and imipramine on polysomnography in healthy subjects.

Polysomnography was performed on eight healthy men with trazodone hydrochloride, imipramine and placebo. Trazodone hydrochloride increased slow wave sleep significantly. Imipramine prolonged rapid eye movement (REM) latency and decreased the percentage of REM sleep significantly. Trazodone decreased stages 1 and 2 sleep, while imipramine increased it. These findings suggest that the antidepressive effect of trazodone might be different from that of imipramine with the suppression of REM sleep.

Adult↗
PubMed2001

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine.

OBJECTIVE: To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine. PATIENTS AND METHODS: The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night). RESULTS: Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004). CONCLUSIONS: We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.

Administration, Oral↗
PubMed2002

The role of imipramine therapy in bladder exstrophy after bladder neck reconstruction.

OBJECTIVE: To assess the role of imipramine therapy after bladder neck reconstruction in patients with bladder exstrophy. PATIENTS AND METHODS: Seventeen children with bladder exstrophy who achieved partial continence after bladder neck reconstruction received imipramine (1.5-2 mg/kg body weight) for a mean duration of 9.5 months. Assessment before and after therapy included an objective classification of the continence status and artificial slow-fill cystometry. RESULTS: Eleven of the 17 patients had a good clinical response to imipramine, with an increase in the continent period to > 2 h, and in nocturnal continence. The urodynamic findings showed a significant improvement in the capacity, end-fill pressure, uninhibited contractions and '20 below' capacity. Only minor side-effects of the drug were reported. CONCLUSION: Imipramine has a role in patients who achieve partial continence after reconstruction, and who have a moderately small capacity bladder with poor compliance and uninhibited contractions.

Antidepressive Agents, Tricyclic↗
PubMed1998

Low dose imipramine improves chest pain but not quality of life in patients with angina and normal coronary angiograms.

AIMS: We investigated patients with chest pain and normal coronary angiograms to determine whether low dose imipramine prescribed as add-on therapy to conventional anti-anginals reduced the incidence of chest pain and whether this led to an overall improvement in quality of life. METHODS AND RESULTS: We performed a randomized, double-blind, cross-over trial of imipramine 50 mg daily vs placebo in 18 women (median age 53 years; range 35-72) with chest pain and normal coronary angiograms who were suffering at least two anginal episodes per week despite conventional anti-anginal medication. Each treatment phase lasted 5 weeks and the incidences of chest pain and side effects were carefully recorded. Quality of life was monitored using a validated health profile questionnaire scoring perceived distress in six domains (pain, energy, mobility, sleep, emotional reactions and social isolation). The total number of chest pain episodes was significantly less during active treatment compared to placebo [11 (3-22) vs 21 (16-28)--median (interquartile range); P = 0.01]. However, a high incidence (83%) of side effects was reported during active treatment and three patients had to be withdrawn from the study as a consequence. No significant improvement was detected in any of the six quality of life domains when imipramine was compared to placebo. CONCLUSION: Imipramine reduces the incidence of chest pain in patients with chest pain and normal coronaries who remain symptomatic despite conventional anti-anginal therapy. The failure to demonstrate associated improvements in quality of life may have been due to the high incidence of side effects.

Adult↗
PubMed1991

Minaprine and dose response in depression. An investigation of two fixed doses of minaprine compared with imipramine.

One hundred and twelve patients suffering from moderate to severe major depression (DSM III) were enrolled into a study to compare the antidepressant activity and side effect profiles of two dosage groups of minaprine (200 mg and 300 mg per day) and one of imipramine (150 mg per day) in psychiatric practice. Eight patients were withdrawn because of unwanted effects (four imipramine, one minaprine 200 mg, three minaprine 300 mg) and seventy-eight spontaneous reports of unwanted effects were made from the imipramine group compared with sixty-four from the minaprine 200 mg and forty-six from the minaprine 300 mg groups. The main efficacy analysis was carried out at 4 weeks on the 89 evaluable patients who completed 2 weeks active treatment, the last observation being carried forward in those patients who did not complete. A secondary analysis was also carried out at 6 weeks. The response in all three treatment groups showed a significant improvement from the severity at entry to the study, and the response rate to minaprine 200 mg daily was similar to that of imipramine (53% vs 54% achieving a reduction of 50% or more on the Hamilton Depression Rating Scale by week 6), although, given the small group sizes, similar efficacy cannot be claimed. In the intention to treat analysis there was a significant dose response relationship with significantly more patients in the lower minaprine 200 mg dose group achieving 50% or more reduction in the Hamilton Rating Scale than the minaprine 300 mg group at week 4 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A comparison of moclobemide and imipramine in treatment of depression.

Moclobemide, a new reversible anti-MAO drug, was compared to imipramine in forty patients with major depression or dysthymic disorder. After a one-week wash-out period, patients were randomly allocated to the two treatment groups, receiving imipramine 25 mg tablets or Moclobemide 50 mg capsules for 28 days. Efficacy and tolerability were investigated by means of HRSD, CGI and VAS at baseline and thereafter at days 3, 7, 14 and 28. All patients completed the study, mean daily doses were 112.5 mg imipramine and 215 mg Moclobemide at day 28. Both treatments had similar antidepressant efficacy and a very good tolerability profile. Moclobemide was superior to imipramine in mean time to onset of effect (7.3 days versus 11.6 days: p less than 0.05) and in mean time to peak effect (13.5 days versus 18.5 days: 0.10 greater than p greater than 0.05. It is concluded that Moclobemide is a safe and effective anti-MAO drug, with an increasing rapid onset of therapeutic activity.

Adult↗
PubMed1988

Efficacy and tolerance of femoxetine and imipramine in the treatment of depressive states. A randomized, double-blind study.

Fifty-two patients with depressive illness characterized by four symptoms (periodical course, psychomotor retardation, diurnal variation, unrealistic self-depreciation) and a score of at least 18 on the Hamilton Depression Scale 1-17 (HDS) were allocated to a double-blind randomized study with femoxetine and imipramine. Patients were diagnosed according to RDC and further classified according to the Newcastle-II index. During the six weeks of treatment, efficacy was evaluated by means of HDS and a global evaluation. Side-effect symptoms were recorded on a check-list by questioning. After six weeks of treatment with femoxetine or imipramine (recommended daily standard dosages are 600 mg femoxetine and 150 mg imipramine (b.i.d.); in the present study, dosages were flexible and could be adjusted according to effect/side-effects) evaluation of efficacy based on HDS, a six-item subscale, groups of HDS items as well as single items showed no statistically significant differences between the treatment groups except with regard to the factor for sleep disturbances in the HDS, where greatest reduction was seen in the femoxetine group. No statistically significant differences regarding side-effect profile were seen. However, in the imipramine group, higher frequencies of such moderate to severe symptoms as dry mouth, constipation and urination difficulties were observed (the greatest difference was seen for dry mouth, p 0.1, while p-values for the remaining two symptoms were greater than 0.1). Moreover, based on the patients' own opinion on side-effects, femoxetine seemed to be better tolerated. One patient took an overdosage of approx. 26 g femoxetine; half of the intake was removed by gastric emptying at the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2000

Laser treatment of imipramine-induced hyperpigmentation.

BACKGROUND: Blue or slate-gray hyperpigmentation is seen with a variety of medications, including imipramine. We describe a patient with significant imipramine-induced pigmentation. OBJECTIVE: The purpose of this study was to describe an effective laser treatment resulting in improvement of imipramine-induced hyperpigmentation, without discontinuing the medication. METHODS: The patient underwent treatment with carbon dioxide, erbium, alexandrite, and ruby lasers to hyperpigmented areas. Tissue biopsy specimens taken before treatment, immediately after treatment with the alexandrite laser, and at clearing were analyzed by light microscopy. RESULTS: The Q-switched alexandrite and ruby lasers resulted in clinical improvement in the patient's hyperpigmentation and a decrease in pigment granules on light microscopy. CONCLUSION: Both the Q-switched alexandrite and ruby lasers are effective treatments for imipramine-induced hyperpigmentation. The improvement is progressive with successive sessions.

Aged↗
PubMed2005

Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine.

Phospholipidosis is the excessive accumulation of intracellular phospholipids in cell lysosomes. Drugs that induce this disease often share common physiochemical properties and are collectively classified as cationic amphiphilic drugs (CADs). Although the cause of phospholipidosis and morphologic appearance of affected lysosomes have been studied extensively, less is known about the physiologic effects of the condition. In the current study, U-937 cells were incubated with the CADs amiodarone (2.5-10 microg/mL) and imipramine (2.5-20 microg/mL). Treatment of U-937 cells with these compounds for 96 h resulted in concentration-related increases in phospholipids, as assessed by flow cytometry using the fluorophore nile red. These results were verified by measuring the concentrations of choline-derived phospholipids, which were significantly increased in drug-treated cells. Cell number in amiodarone (10 microg/mL) and imipramine (20 microg/mL) cultures following the 96-h incubation period were markedly reduced compared to control cultures. These observations suggested that accumulation of cellular phospholipids could inhibit cell proliferation. Flow cytometric analysis revealed a decrease in the percentage of cells in the S-phase of the cell cycle following drug treatment, yet DNA replication still occurred in a significant portion of cells. Interestingly, amiodarone and imipramine induced apoptosis in U-937 cells as shown by annexin V-FITC staining and DNA fragmentation. Enzymatic assays demonstrated that amiodarone and imipramine induced the activity of caspases 2 and 3. These results suggest that disruption of cell lysosomes in U-937 cells following accumulation of phospholipids does not cause a cell cycle arrest but instead induces apoptosis by activation of caspase pathways.

Amiodarone↗
PubMedDate not supplied

Comparison of a new GLC-AFID method with a GLC-MS selected ion monitoring technique and a radioimmunoassay for the determination of plasma concentrations of imipramine and desipramine.

A gas-liquid chromatographic procedure employing an alkali flame ionization detector (GLC-AFID) for the quantitation of imipramine and its major active metabolite, desipramine, in plasma was developed. This method validated a previously reported radioimmunoassay for imipramine and desipramine. The GLC-AFID method was also compared with a GLC-mass spectrometric procedure which employed selected ion monitoring (GLC/MS-SIM) in which specific ions for imipramine and desipramine were monitored. The two methods using gas chromatographic separation were shown to be suitable for therapeutic monitoring of these drugs in patients. The direct immunoassay, which measures the total imipramine plus desipramine, is very useful when large numbers of samples are to be analysed rapidly and it compares favorably with the other two analytical procedures.

Desipramine↗
PubMed2001

Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome.

BACKGROUND: Primary fibromyalgia syndrome (PFS) is a chronic disorder commonly seen in rheumatological practice. The pathophysiological disturbances of this syndrome, which was defined by the American College of Rheumatology in 1990, are poorly understood. This study evaluated, in 30 patients, the hypothesis that PFS is a pain modulation disorder induced by deregulation of serotonin metabolism. OBJECTIVES: To compare platelet [(3)H]imipramine binding sites and serotonin (5-HT) levels in plasma-rich platelets (PRP) of PFS patients with those of matched healthy controls and to compare the levels of biogenic amine metabolites in the cerebrospinal fluid (CSF) of PFS patients with those of matched controls. METHODS: Platelet [(3)H]imipramine binding sites were defined by two criteria, B(max) for their density and K(d) for their affinity. PRP 5-HT and CSF metabolites of 5-HT (5-hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3-methoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were assayed by reversed-phase high-performance liquid chromatography with coulometric detection. RESULTS: [(3)H]Imipramine platelet binding was similar (P=0.43 for B(max) and P=0.30 for K(d)) in PFS patients (B(max)=901+/-83 fmol/mg protein, K(d)=0.682+/-0.046) and in matched controls (B(max)=1017+/-119 fmol/mg protein, K(d)=0.606+/-0.056). PRP 5-HT was significantly higher (P=0.0009) in PFS patients (955+/-101 ng/10(9) platelets) than in controls (633+/-50 ng/10(9) platelets). When adjusted for age, the levels of all CSF metabolites were lower in PFS patients. The CSF metabolite of norepinephrine (MHPG) was lower (P:=0.003) in PFS patients (8.33+/-0.33 ng/ml) than in matched controls (9.89+/-0.31 ng/ml) and 5-HIAA was lower (P=0.042) in PFS female patients (22.34+/-1.78 ng/ml) than in matched controls (25.75+/-1.75 ng/ml). For HVA in females, the difference between PFS patients (36.32+/-3.20 ng/ml) and matched controls (38.32+/-2.90 ng/ml) approached statistical significance (P=0.054). CONCLUSION: Changes in metabolites of CSF biogenic amines appear to be partially correlated to age but remained diagnosis-dependent. High levels of PRP 5-HT in PFS patients were associated with low CSF 5-HIAA levels in female patients but were not accompanied by any change in serotonergic uptake as assessed by platelet [(3)H]imipramine binding sites. These findings do not allow us to confirm that serotonin metabolism is deregulated in PFS patients.

Biogenic Amines↗
PubMed1989

A double-blind comparative study: amineptine (Survector 100) versus imipramine.

The aim of the study was to compare the antidepressant effects of amineptine with imipramine in depressive illness. According to the DSM-III criteria, 33 patients diagnosed as having depressive illnesses were given either imipramine or amineptine, 50-100 mg and 100-200 mg, respectively, per day on a double-blind basis over a period of 2 months. Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Hamilton and Montgomery and Asberg Depression Rating Scales and Clinical Global Impression Scale. Amineptine produced fewer anticholinergic effects than imipramine. The results show that amineptine, as well as imipramine, is well suited for treating depressed patients.

Adult↗
PubMed1994

Effects of moclobemide on depressive symptoms and cognitive performance in a geriatric population: a controlled comparative study versus imipramine.

Moclobemide, a novel monoamine oxidase-A reversible inhibitor with demonstrated antidepressive efficacy, was administered double-blind versus imipramine to aged depressive subjects. The two drugs were given for 60 days in increasing doses up to 600 mg for moclobemide and 100 mg for imipramine. Fifteen patients received moclobemide and 15 received imipramine. Psychiatric conditions and symptoms were rated at 0, 7, 14, 30, 45, and 60 days after the beginning of the trial by means of the Scale for the Assessment of Psychoorganic Syndromes, Hamilton Rating Scale for Depression, Rome. Depression Inventory, Hamilton Anxiety Rating Scale, State-Trait Anxiety Inventory-X form, and the Clinical Global Impression Scale. Cognition was tested through the Benton visual retention test at days 0, 30, and 60 and the Digit Substitution Test of the Wechsler Adult Intelligence Scale at days 0 and 60. Side effects were assessed through the Dosage Record Emergent Symptoms at days 0, 7, 14, 30, 45, and 60. The dropout rate was significantly greater in the moclobemide group. Both drugs induced an improvement in depressive and anxious symptomatology, with moclobemide showing a faster onset. Furthermore, moclobemide showed an enhancing effect on cognition, which was not shown by imipramine. Such results indicate that moclobemide could prove to be the drug of choice in geriatric depression, given that cognitive effects are prominent in the aged.

Aged↗
PubMed1992

Imipramine treatment of children with separation anxiety disorder.

The efficacy of imipramine was investigated in 20 children (ages 6 to 15) with separation anxiety disorder. Children were treated for a month with vigorous behavioral treatment. If they did not respond, they entered a double-blind, randomized, 6-week trial of imipramine or placebo. Of 45 children accepted, 21 (47%) entered the trial. About half the children improved with either treatment, and no superiority for imipramine was obtained. There was no instance of clinically significant EKG changes. This small study failed to replicate previous findings of imipramine efficacy in a similar, but larger, clinical population.

Adolescent↗
PubMed1990

Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind, placebo-controlled trial.

Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.

Adult↗
PubMed1995

Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adult and elderly subjects.

The acute and subchronic effects of two dosages of a new serotonergic antidepressant, nefazodone, and those of the tricyclic imipramine were examined in a double-blind, crossover, placebo-controlled study. Twenty-four healthy subjects from two age groups (12 adults and 12 elderly from both sexes) received the four treatments (nefazodone, 100 and 200 mg twice daily; imipramine, 50 mg twice daily; and placebo) for 7 days with a 7-day washout period. Measurements were performed after the morning doses on day 1 and day 7. These included a standard over-the-road highway driving test, a psychomotor test battery, and sleep latency tests. Blood samples were taken on both days and analyzed to determine concentrations of parent drugs and their major metabolites. The main results showed that the reference drug, imipramine, had a detrimental effect after a single dose on lateral position control in the driving test, primarily in the adult group, that diminished after repeated dosing. Minor impairment on psychomotor test performance was found with both days. On the other hand, a single administration of both doses of nefazodone did not impair highway driving performance (even showed some improvement) and had no or only minor effects on psychomotor performance. After repeated dosing, nefazodone 200 mg twice daily (but not the 100-mg dose) produced slight impairment of lateral position control; dose-related impairment of cognitive and memory functions was found. The effects of nefazodone were generally in the same direction in both age groups. Significant correlations were found between steady-state concentrations of nefazodone in plasma (200-mg, twice-daily condition) as well as imipramine, and reaction time changes in a memory scanning task. Neither drug appeared to induce daytime sleepiness as measured by the sleep latency tests.

Adult↗
PubMed1987

Fluvoxamine and imipramine: results of a long-term controlled trial.

Following a multicentre double-blind controlled trial comparing the effects of fluvoxamine and imipramine in depressed inpatients (M.D.E.) 39 patients continued on longer term treatment with maintenance of double-blind conditions (17 on fluvoxamine, 22 on imipramine). The results regarding the reasons for premature interruption of treatment show a slight advantage in favour of fluvoxamine. There were several significant differences in favour of fluvoxamine at the 20th week. The most common side-effects were hot flushes with imipramine and dizziness with fluvoxamine. Overall, despite the small number of patients, the results show a greater clinical tolerance to fluvoxamine than to imipramine.

Antidepressive Agents↗
PubMed1989

A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression.

Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant to be marketed in the U.S. In this double-blind trial fluoxetine was compared with imipramine and placebo among 198 outpatients with DSM-III major depression, of whom 145 completed at least 2 weeks of active treatment and were evaluated for efficacy. Significantly fewer patients in each active drug group terminated early due to lack of efficacy compared to placebo. Both imipramine and fluoxetine were significantly superior to placebo on most measures. There were no consistently significant differences between the two active drugs although a trend favored imipramine on a number of measures. Fluoxetine was generally well tolerated. Significantly more imipramine than placebo patients terminated early due to side-effects while the fluoxetine-placebo difference was not significant. The results support previous studies which suggest fluoxetine's superior side-effect profile and the approximate antidepressant equivalence of fluoxetine and TCAs.

Adult↗