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PubMed1995

Specific binding of [3H]imipramine indicates the presence of a specific serotonin transport system on endothelial cells of porcine brain.

The blood-brain barrier (BBB) represents a complex epithelial interface in vertebrates that separates the blood compartment from the extracellular fluid compartment of the brain. Isolated microvessels are a tool to study the function of this interface in vitro. Here we report on attempts to demonstrate the presence of the serotonin transporter on microvessels from the porcine brain. For comparison, membrane preparations of brain tissue were used. The enrichment of the microvessel fraction determined by measurement of alkaline phosphatase activity was about 30-fold. In saturation experiments high- and low-affinity binding of [3H]imipramine could be demonstrated on brain microvessels. Different concentrations of unlabelled imipramine were used to inhibit the binding of [3H]imipramine in brain tissue and microvessels. Comparison of both preparations revealed a two-fold higher density of the high-affinity binding site, while the density of the low-affinity binding site was 28-fold higher in brain microvessels. Imipramine binding could be inhibited by potent non-tricyclic inhibitors of the serotonin transporter such as paroxetine and fluoxetine but also by the tricyclic antidepressant drugs clomipramine and desipramine. Therefore, it is concluded that [3H]imipramine labels serotonin uptake sites localized on porcine brain microvessels.

Animals↗
PubMed1995

The hypoalgesic effect of imipramine in different human experimental pain models.

In a randomized, placebo-controlled, double-blind, cross-over study, the hypoalgesic effect of a single oral dose of 100 mg imipramine was investigated in 12 healthy volunteers. Test procedures performed before, 3, 6, and 9 h after medication included determination of (1) pain detection and tolerance thresholds to heat and pressure; (2) the thresholds of quadriceps femoris muscle withdrawal reflex to single and repeated electric stimulation of the sural nerve; (3) amplitude of the reflex evoked by 1.5 times the premedication reflex threshold; and (4) continuous pain rating during the cold pressor test. Imipramine significantly increased pain tolerance thresholds to heat (P = 0.03) and pressure (P = 0.01), and both the psychophysical pain tolerance threshold and the reflex threshold to single electric stimulation (P = 0.02 and P = 0.03, respectively). On the repeated stimuli, which consisted of 4 pulses given at 3 Hz, imipramine induced a significant increase in the threshold at which the pain summated through the stimulation series (P = 0.03), whereas the increase in the threshold at which the reflex summated was not significant (P = 0.09). Pain detection thresholds to heat and pressure, the amplitude of the reflex to single suprathreshold stimulation, and pain ratings during the cold pressor test were unaltered by imipramine. It is concluded that imipramine has a differential hypoalgesic effect on different human experimental pain tests. This provides new possibilities of assessing the differential effect of different tricyclic antidepressants on different pain modalities and intensities.

Adolescent↗
PubMed1982

Pharmacological comparison of the potential antidepressant UP 614-04 with viloxazine and imipramine; behavioral studies.

1. Several behavioral tests were used to compare the pharmacological activity of the potential antidepressant UP 614-04 with those of viloxazine and imipramine. 2. Orally-administered UP 614-04, like viloxazine, reduced locomotor activity in mice, and, like viloxazine and imipramine, it antagonized the hypothermia or ptosis induced by reserpine or tetrabenazine and the hypothermia induced by a high dose of apomorphine. 3. UP 614-04 antagonized oxotremorine-induced hypothermia, and to a lesser extent, oxotremorine-induced tremors, indicating that it possesses some CNS anticholinergic activity. 4. Both imipramine and viloxazine were more potent than UP 614-04 in potentiating yohimbine toxicity in mice. 5. Orally-administered UP 614-04 potentiated d-amphetamine-induced stereotypy to a greater extent than viloxazine, but to a lesser extent than imipramine. 6. Intraperitoneally-injected UP 614-04 was much more potent than viloxazine in increasing tryptamine convulsive potential in rats, indicating that it might exert an inhibitory action on monoamine oxidase. 7. These results indicate that UP 614-04 has a behavioral profile that is consistent with an antidepressant action, but that it differs from imipramine and viloxazine.

Animals↗
PubMed1983

Autoradiographic localization of [3H]-imipramine binding sites: association with serotonergic neurons.

Localization of the binding sites for a radioactive form of the tricyclic antidepressant imipramine has been accomplished using receptor autoradiographic techniques. These studies demonstrated a marked overlap between regions presenting dense concentrations of imipramine binding sites and regions known to receive serotonergic projections. Lesions of the serotonergic neurons were created by intracerebroventricular injections of the potent neurotoxin 5,7-dihydroxytryptamine. The effectiveness of these lesions was ascertained by immunohistochemical localization of serotonin containing neurons in both lesioned and vehicle treated control animals. Animals lesioned in this fashion, showed a dramatic loss of imipramine binding sites in all of the areas which were previously densely labeled. The catecholamine containing neurons were lesioned in another group of animals using 6-hydroxydopamine. The effects of these lesions were ascertained using fluorescence histochemical techniques. In these animals, the imipramine binding sites were unaltered. These results suggest that imipramine binding sites are presynaptic and are located on serotonin containing terminals and not on catecholamine containing neurons.

5,7-Dihydroxytryptamine↗
PubMed2004

Long-term imipramine withdrawal induces a depressive-like behaviour in the forced swimming test.

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania. In a recent study we have shown a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal. We interpreted this result suggesting that the mood-switches observed in bipolar patients following antidepressant treatment and subsequent withdrawal, i.e. mania followed by rebound depression, might depend upon parallel changes in the mesolimbic dopamine system sensitivity. On this basis, one might predict a depressive-like behaviour after long-term interruption of a chronic treatment with imipramine. To test this hypothesis we examined the behaviour of rats treated with chronic imipramine 40 days after treatment interruption in an animal model of depression, the forced swimming test. The results show that animals treated with chronic imipramine, 40 days after treatment interruption, display a depressive-like behaviour in the forced swimming test, as indicated by their increased immobility with respect to the control group.

Animals↗
PubMed2005

Action of imipramine on activated ATP-sensitive K(+) channels in interstitial cells of Cajal from murine small intestine.

Tricyclic antidepressants have been widely used for the treatment of depression and as a therapeutic agent for the altered gastrointestinal (GI) motility of irritable bowel syndrome (IBS). The aim of this study was to clarify whether antidepressants directly modulate pacemaker currents in cultured interstitial cells of Cajal (ICC). We used the whole-cell patch-clamp techniques at 30 degrees C in cultured ICC from the mouse small intestine. Treatment of pinacidil, an ATP-sensitive K(+) channel opener, in the ICC using the current clamping mode, produced hyperpolarization of the membrane potential and decreased the amplitude of the pacemaker potentials. With the voltage clamp mode, we observed a decrease in the frequency and amplitude of pacemaker currents and increases in the resting outward currents. These effects of pinacidil on pacemaker potentials and currents were completely suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. Also, with the current clamp mode, imipramine blocked the affect of pinacidil on the pacemaker potentials. Observations of the voltage clamp mode with imipramine, desipramine and amitryptyline suppressed the action of pinacidil in the ICC. Next, we examined whether protein kinase C (PKC) and the G protein are involved in the action of imipramine on pinacidil induced pacemaker current inhibition. We used chelerythrine, a potent PKC inhibitor and GDPbetaS, a nonhydrolyzable guanosine 5-diphosphate (GDP) analogue that permanently inactivates GTP-binding proteins. We found that pretreatment with chelerythrine and intracellular application of GDPbetaS had no influence on the blocking action of imipramine on inhibited pacemaker currents by pinacidil. We conclude that imipramine inhibited the activated ATP-sensitive K(+) channels in ICC. This action does not appear to be mediated through the G protein and protein kinase C. Furthermore, this study may suggest another possible mechanism for tricyclic antidepressants related modulation of GI motility.

ATP-Binding Cassette Transporters↗
PubMed2005

Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene promoter activity operates through a PI3-K/AKT mediated pathway.

Antidepressant drugs inhibit the corticotropin-releasing-hormone (CRH) gene promoter activity in the differentiated Neuro-2A cells, but a molecular mechanism of their action has been poorly recognized. The aim of the present study was to elucidate the involvement of some intracellular signal transduction pathways in imipramine-induced inhibition of CRH gene activity in the differentiated Neuro-2A cells, stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It was found that wortmannin (0.1muM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K) and forskolin (10, 25muM), an activator of adenylate cyclase enhanced the basal activity of CRH gene promoter, whereas inhibitors of protein kinase A, calcium/calmodulin kinase (CaMK) and mitogen-activated protein kinase (MAPK) had opposite effects. Moreover, wortmannin at a low concentration (0.01muM) significantly reversed the inhibitory effect of imipramine on CRH-CAT activity, whereas other protein kinase inhibitors were inactive or even enhanced the imipramine effects. The involvement of PI3-K/Akt pathway in the imipramine action was confirmed by Western blot study, which showed that this drug increased phospho-Ser-473 Akt level, but had no effect on total Akt and glycogen synthase kinase (GSK-3beta) levels. These results indicate that the inhibitory effect of imipramine on the CRH gene promoter activity in Neuro-2A cells is mainly connected with enhancement of PI-3K/Akt pathway.

Adrenergic Uptake Inhibitors↗
PubMed2002

Adaptation of monoaminergic responses to phencyclidine in nucleus accumbens and prefrontal cortex following repeated treatment with fluoxetine or imipramine.

The adaptive neuronal changes that follow chronic administration of antidepressant drugs are thought to underlie clinical improvement in patient populations. Recent evidence suggests that alterations specific to N-methyl-D-aspartate (NMDA) receptors may be a final common pathway to antidepressant action. To investigate this possibility, we sought to establish the effects of chronic fluoxetine or imipramine treatment on the monoamine stimulating effect of the non-competitive NMDA antagonist phencyclidine. Male, Sprague-Dawley rats (n=9/group) were treated with saline (1 ml/kg, i.p.), imipramine (10 mg/kg, i.p.) or fluoxetine (10 mg/kg, i.p.) once daily for 14 consecutive days. After a 7-day drug-free period, animals given an acute challenge of either saline or phencyclidine (5 mg/kg, i.p.). One hour later, animals were killed, brains were removed, and the prefrontal cortex, striatum, and nucleus accumbens were dissected. Samples were assayed for the monoamines and their primary metabolites by HPLC. Repeated treatment with fluoxetine or imipramine did not alter baseline dopamine or serotonin turnover. Acute phencyclidine treatment increased prefrontal cortex and nucleus accumbens dopamine turnover in saline-treated animals (P<0.01); however, the effect in the nucleus accumbens was prevented in animals pretreated with imipramine or fluoxetine. Acute phencyclidine challenge also increased serotonin turnover in prefrontal cortex of saline- or imipramine-pretreated rats (P<0.01), though this effect was attenuated in animals pretreated with fluoxetine. Overall, the data suggest that repeated antidepressant treatment alters monoamine turnover in specific brain regions in response to blockade of NMDA receptors. The data highlight the importance of adaptive responses to NMDA receptors resulting from chronic antidepressant treatment.

Adaptation, Physiological↗
PubMed2003

Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal.

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania, which in turn, might be involved in the development of rapid cycling in bipolar patients. In this study, we investigated the changes occurring in the sensitivity of the mesolimbic dopamine system up to 40 days after antidepressant withdrawal. Male Sprague-Dawley rats were treated for 3 weeks with imipramine (20 mg/kg) and tested for motor activity 24 h, 12, 33 and 40 days after treatment withdrawal. Ambulatory activity and rearing counts were recorded after challenge with the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Imipramine increased the motor response to quinpirole, 24 h after treatment discontinuation. No relevant differences between the groups were found after 12 and 33 days. After 40 days, a decreased level of rearing was observed in the group treated with imipramine. These results show a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal and suggest that the mood-switches observed in bipolar patients following antidepressant treatment and subsequent withdrawal, i.e. mania followed by rebound depression, might depend upon parallel changes in the mesolimbic dopamine system sensitivity.

Analysis of Variance↗
PubMed1998

Differential effects of chronic imipramine and fluoxetine on basal and amphetamine-induced extracellular dopamine levels in rat nucleus accumbens.

The effect of chronic treatment with the tricyclic antidepressant drug, imipramine (10 mg/kg per day), the selective serotonin (5-HT) reuptake inhibitor, fluoxetine hydrochloride (10 mg/kg per day), and vehicle, in drinking water for 24-28 days followed by 3-5 days withdrawal, on extracellular dopamine levels was studied in rat nucleus accumbens by in vivo microdialysis. Basal extracellular dopamine levels in the nucleus accumbens were increased after chronic imipramine (12.7 +/- 1.5 fmol/20 microl per 30 min, P = 0.019), and moderately decreased after chronic fluoxetine (6.5 +/- 0.6, P = 0.047), as compared to the vehicle controls (9.1 +/- 0.7), determined by one-way analysis of variance (ANOVA). Repeated measure ANOVA indicated that the D-amphetamine sulfate (0.5 mg/kg, s.c.)-induced increase in extracellular dopamine levels in the nucleus accumbens was potentiated after chronic imipramine (P = 0.002), but unchanged after chronic fluoxetine (P = 0.83). The difference in the effect of amphetamine could be influenced by the significant differences in basal levels. However, these results were also confirmed by analysis of the net area under the curve (net-AUC) for a 180-min period (six samples): for chronic imipramine (337 +/- 45 fmol/180 min, P = 0.005) and chronic fluoxetine (249 +/- 38, P = 0.57), as compared to the vehicle controls (178 +/- 29), determined by one-way ANOVA. We suggest that the effect of treatment with these agents on mesolimbic dopamine is unlikely to be involved in their shared antidepressant action, but may be relevant to other aspects of the therapeutic profile of these two drugs, e.g. the switch into mania which is more common after treatment with imipramine than fluoxetine and exacerbation of positive symptoms in patients with schizophrenia or schizoaffective disorder.

Amphetamine↗
PubMed2002

Imipramine treatment up-regulates the expression and function of mGlu2/3 metabotropic glutamate receptors in the rat hippocampus.

We examined the effect of a chronic imipramine treatment (10 mg/kg, i.p., once daily for 21 days) on the expression and function of metabotropic glutamate (mGlu) receptors in discrete regions of the rat brain. Chronic imipiramine treatment up-regulated the expression of mGlu2/3 receptor proteins in the hippocampus, nucleus accumbens, cerebral cortex and corpus striatum. Expression of mGlu1a receptor protein was increased exclusively in the hippocampus, whereas no changes in the expression of mGlu4 and mGlu5 receptors or Homer-1a protein were detected. Using hippocampal slices, we examined the stimulation of polyphosphoinositide (PI) hydrolysis induced by mGlu receptor agonists in control and imipramine-treated rats. Imipramine treatment amplified the PI response to the non subtype-selective mGlu receptor agonist, 1S,3R-aminocyclopentane-1,3-dicarboxylated (1S,3R-ACPD) in both hippocampal and cortical slices, but failed to affect the response to the selective mGlu1/5 receptor agonist, S-3,5-dihydroxyphenylglycine (DHPG). Amplification was restored when DHPG was combined with the selective mGlu2/3 receptor agonist, LY379268. In addition, 1S,3R-ACPD-stimulated PI hydrolysis was no longer enhanced in imipramine-treated rats when the mGlu2/3 component of the PI response was abrogated by the antagonist, LY341495. In contrast, the ability of LY379268 to inhibit forskolin-stimulated cAMP formation was reduced in hippocampal slices of rats chronically treated with imipramine. Taken together, these results suggest that neuroadaptive changes in the expression and function of mGlu2/3 receptors occur in response to chronic antidepressants.

Adrenergic Uptake Inhibitors↗
PubMed2000

Paradoxical effect of imipramine in hyperprolactinemic female rats exposed to the forced swimming test.

This study was designed to investigate the effect of hyperprolactinemia, with high or low estrogen levels, on the response to imipramine in the forced swimming test. Three groups of female rats were studied: (1) ovariectomized controls, with low serum prolactin (PRL) and estrogen levels, (2) ovariectomized, estrogen-treated rats, with high PRL and high estrogen levels, and (3) pituitary-grafted rats, with high PRL and low estrogen levels. The hyperprolactinemic groups did not show significant behavioral changes in the forced swimming test preceded by saline injection. Imipramine decreased the immobility time by 37.5% in ovariectomized controls but not in the pituitary-grafted group, and there was an increment of 48.4% in immobility time following imipramine administration in the estrogen-treated group (p<0.05). This paradoxical response to imipramine was significantly correlated with serum PRL (r = 0.59, p<0.01) but not with estradiol levels. These findings suggest that, at least in female rats submitted to the forced swimming model, PRL may induce reversed behavioral effects in response to imipramine, independently of circulating estrogen levels.

Animals↗
PubMedDate not supplied

Influence of ACTH on the effects of imipramine, desipramine and lithium on duration of immobility of rats in the forced swim test.

We examined the effects of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test with the administration of imipramine, desipramine, or lithium. A single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) significantly decreased the duration of immobility in normal rats in a dose-dependent manner. Lithium (10-100 mg/kg, p.o.), however, had no affect on the performance of rats in the forced swim test. ACTH (100 microg/day), administered subcutaneously to rats for 1, 3, 7, and 14 days, had no apparent effect on the duration of immobility in this test. The immobility-decreasing effect induced by a single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) was blocked by chronic administration of ACTH for 3-14 days. The reduction of immobility, induced by chronic administration of imipramine (10 mg/kg, i.p.) for 15 days, was blocked by treatment with ACTH for 14 days. When lithium (100 mg/kg, p.o.) was administered for 15 days concurrently with imipramine (10 mg/kg, i.p.), we observed a significant decrease in immobility in rats treated with ACTH for 14 days. We suggest that chronic treatment of rats with ACTH may prove to be an effective model of tricyclic antidepressants-treatment-resistant depression.

Animals↗
PubMed2002

Effects of imipramine and lithium on wet-dog shakes mediated by the 5-HT2A receptor in ACTH-treated rats.

We examined the influence of imipramine and lithium on wet-dog shakes induced by the (+/-)-DOI, 5-HT2A receptor agonist in adrenocorticotropic hormone (ACTH)-treated rats. The administration of imipramine for 14 days decreased the (+/-)-DOI-induced wet-dog shakes response; chronic administration of lithium for 14 days, however, had no effect. Chronic ACTH (100 microg/rat sc) treatment increased the wet-dog shake response induced by (+/-)-DOI. This effect of ACTH for 14 days, increasing the (+/-)-DOI-induced wet-dog shakes, was not inhibited by a 14-day administration of imipramine. Chronic coadministration of imipramine and lithium, lasting 14 days, decreased the wet-dog shakes response induced by (+/-)-DOI in rats treated with ACTH for 14 days. These findings indicate that lithium inhibits the hyperfunction of the 5-HT2A receptor in rats treated with ACTH when coadministered with imipramine.

Adrenocorticotropic Hormone↗
PubMed2002

Chronic imipramine enhances 5-HT(1A) and 5-HT(2) receptors-mediated inhibition of panic-like behavior in the rat dorsal periaqueductal gray.

Electrical stimulation of the dorsal periaqueductal gray (DPAG) has been used to induce panic-like behavior in rats. In the present study, we investigated the effect of chronic imipramine treatment on the sensitivity of different 5-HT receptor subtypes in inhibiting aversion induced by electrical stimulation of this brain area. For that, the effects of intra-DPAG administration of the endogenous agonist 5-HT (20 nmol), the 5-HT(1A) receptor agonist 8-OH-DPAT (8 nmol) and the 5-HT(2A/2C) receptor agonist DOI (16 nmol) were measured in female Wistar rats given either chronic injection of imipramine (15 mg/kg, 3 weeks, ip) or saline. The results showed that the three receptor agonists raised the threshold of aversive electrical stimulation in both groups of animals, but this antiaversive effect was significantly higher in rats treated with imipramine. Treatment with imipramine did not change the basal threshold of aversive electrical stimulation measured before intra-DPAG injection of the 5-HT agonists. The results suggest that sensitization of both 5-HT(1A) and 5-HT(2) receptors within the DPAG may be involved in the beneficial effect of imipramine in panic disorder (PD).

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Effect of imipramine on the expression and acquisition of morphine-induced conditioned place preference in mice.

The effect of imipramine and alpha-adrenoceptor agonists and antagonists on the acquisition or expression of morphine-induced conditioned place preference (CPP) was studied in mice. An unbiased CPP paradigm was used to study the effect of the agents. In the first set of experiments, the drugs were used during the development of CPP by morphine or they were used alone in order to see if they induce CPP or conditioned place aversion (CPA). Our data showed that intraperitoneal injection of morphine sulphate (2.5-10 mg/kg) induced CPP in mice. Imipramine (0.5-2.5 mg/kg), phenylephrine (0.5-2 mg/kg), yohimbine (0.5-2 mg/kg) or prazosin (0.1-1 mg/kg) did not influence CPP, but clonidine (0.002-0.05 mg/kg) induced CPA. Yohimbine increased, while clonidine and prazosin reversed, morphine-induced CPP. Phenylephrine did not influence the CPP induced by morphine. In the second set of experiments, when the drugs were used before testing on Day 6, in order to test their effects on the expression of morphine-induced CPP, imipramine (0.5-5 mg/kg) reversed morphine-induced CPP and this reversal was blocked by naloxone (2 mg/kg). Clonidine and prazosin reversed, while yohimbine decreased morphine-induced CPP. Phenylephrine did not alter the morphine response. Furthermore, yohimbine and prazosin reversed the imipramine effect. None of the drugs influenced locomotion. However, prazosin or yohimbine in combination with morphine altered locomotor activity during the acquisition of CPP. Yohimbine by itself increased locomotion. It is concluded that imipramine can induce CPA through an opioid receptor mechanism and alpha-adrenoceptor agents may influence morphine CPP.

Animals↗
PubMed1979

Clinical characteristics of imipramine-induced orthostatic hypotension.

The effects of imipramine hydrochloride on blood-pressure were examined in a prospective and a retrospective study. In a prospective study of 44 depressed patients given imipramine in doses to achieve antidepressant plasma-concentrations there was no effect of the drug on lying blood-pressure. When patients then stood up, the drug produced an average fall in systolic pressure of 26 mm Hg (t = 13.6, P less than 0.001) that was consistent over the four weeks of observation. Contrary to expectation, this fall was independent of patients' age, pre-existing heart-disease, or plasma-level of the drug. The best predictor of orthostatic hypotension during treatment was the degree of orthostatic drop in pressure before treatment (r = 0.695, P less than 0.001). In order to establish the clinical significance of this orthostatic drop in pressure, a retrospective study of 148 depressed patients treated with imipramine was conducted. These 148 patients, average age 59 years, received an average dose of 225 mg of imipramine. Almost 20% of them had symptoms usually associated with orthostatic hypotension that were severe enough to interfere with their treatment: over 4% sustained physical injuries. In our experience orthostatic hypotension is the commonest serious cardiovascular side-effect of imipramine.

Adult↗
PubMed2001

Sertraline versus imipramine to prevent relapse in chronic depression.

BACKGROUND: Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study. METHODS: After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (> or = 2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment. RESULTS: Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients (n = 147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment. LIMITATIONS: The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates. CONCLUSIONS: Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

Adult↗