Desipramine Group Research Articles

Desipramine ameliorates fine particulate matter-induced hepatic insulin resistance by modulating the ceramide metabolism in mice

Recent research has highlighted a correlation between exposure to ambient fine particulate matter (PM2.5) and the development of systemic insulin resistance (IR) along with an elevated risk of diabetes. Ceramide has emerged as one of the pathogenic mechanisms contributing to IR. The inhibition of acid sphingomyelinase (ASMase) activity by desipramine (DES) has been shown to effectively reduce ceramide levels. In the present study, 24 female C57BL/6 N mice were randomized into one of the four groups: the filtered air exposure (FA) group, the concentrated PM2.5 exposure (PM) group, the concentrated PM2.5 treated with low-dose DES (DL) group, and the concentrated PM2.5 treated with high-dose DES (DH) group. The PM, DL and DH groups were exposed to PM2.5 for an 8-week period within a whole-body exposure system. The study encompassed extensive examinations of glucose homeostasis, liver lipid profile, ceramide pathway, and insulin signaling pathway. Our results demonstrated that PM2.5 exposure caused impaired glucose tolerance, elevated ceramide levels, increased phosphorylation PP2A, reduced Akt phosphorylation, and hindered GLUT2 expression. Remarkably, DES administration mitigated PM2.5-induced IR by effectively lowering ceramide levels. In conclusion, the reduction of ceramide levels by DES may be a promising therapeutic strategy for coping PM2.5-induced IR.

Crocin lessens desipramine-induced phospholipidosis biomarker levels via targeting oxidative stress- related PI3K/Akt/mTOR signaling pathways in the rat liver.

Forty adult male rats were divided into 4 groups (n =10): control group, a group receiving intraperitoneal (IP) crocin (50 mg/kg/day), a group receiving IP desipramine (10mg/kg/day), and a group receiving both IP crocin and desipramine. After 3 weeks of treatment, the combined treatment group showed diminished desipramine-induced hepatic phospholipidosis, along with significant reductions in total oxidant status (TOS) , the levels of inflammatory markers including interleukin 6 (IL6) and tumor necrosis factor α (TNF-α) and apoptotic markers including caspase3 and Bcl2 (B-cell lymphoma 2) while other markers including total antioxidant capacity (TAC), superoxide dismutase (SOD), phosphoinositide 3-kinases (PI3K), and mammalian target of rapamycin (mTOR) were increased. The gene expression of lysosomal enzymes including ELOVL6, SCD1 and HMGR was notably downregulated, while AP1S1 was upregulated in the combined treatment group compared to the desipramine group. No ultrastructural signs of hepatic phospholipidosis, in the form of multilamellar bodies, were apparent in the combined treatment group. These data collectively suggest that crocin has a protective effect against desipramine-induced phospholipidosis. (www.actabiomedica.it).

Efficacy of group reality therapy versus desipramine pharmacotherapy in drug craving and relapse of methamphetamine-dependent patients in yazd

Aims: In this comparative study, we aimed to investigate the effectiveness of group reality therapy versus desipramine pharmacotherapy in reducing the craving and relapse of methamphetamine-dependent patients. Methods: This semi-experimental research was conducted using a control group and two experimental groups of reality therapy and desipramine pharmacotherapy. The statistical population of this study included all methamphetamine-dependent patients under methadone treatment who were referred to the health clinics of Yazd city, Iran. We selected 30 patients using convenience sampling and then categorized them randomly into three groups of reality therapy, desipramine pharmacotherapy, and control. In the pre-test stage, the risk questionnaire was administered to evaluate the stimulants. The first experimental group attended 10 reality therapy sessions once a weak and was assessed immediately after the treatment. The data were analyzed using the covariance analysis. Results: The findings showed no significant difference between the total mean score of the reality therapy and desipramine pharmacotherapy groups (F= 3.289, P= 0.087). Hence, these two interventions did not affect attenuating craving to use the drugs. To check the homogeneity presumptions of the covariance matrix and variances of the two groups, the Box (6.241) and Levine (0.250) tests were applied, respectively. The results about the experimental groups (Reality therapy and Desipramine group) compared to the control group were meaningful. Conclusion: There was no significant difference between reality therapy and desipramine pharmacotherapy groups in reducing the craving to use the drugs. The scope of changes showed that craving for drug consumption reduced in reality therapy (51.0) and desipramine pharmacotherapy (36.0) groups.

Protective effects of desipramine on alveolar bone in experimental periodontitis.

Desipramine is a tricyclic antidepressant with immune-modulatory activity, whose effects on ligature-induced periodontitis are yet to be investigated. Hence, its actions on alveolar bone resorption, gingival collagen content and key inflammatory mediators were herewith analyzed. A total of 60 male Wistar rats were randomly assigned into three groups: 1) control: rats without ligature treated with vehicle (saline); 2) ligature: rats with ligature-induced periodontitis treated with vehicle; 3) ligature + desipramine: rats with ligature-induced periodontitis treated with desipramine (20mg/kg/d in vehicle). Mandibles and gingival tissues were collected 3 or 15 days after ligature insertion (or no ligature insertion for controls) and treatments. Alveolar bone resorption and gingival collagen fibers were histologically analyzed using either HE or picrosirius red staining. Gingival mRNA expressions of interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were obtained through reverse transcription polymerase chain reaction. MMP-9 activity was analyzed by zymography. Alveolar bone loss was significantly reduced in the ligature + desipramine group (P<0.05), whereas gingival collagen degradation was like the ligature group (P>0.05). Desipramine administration downregulated mRNA expressions of IL-1β, iNOS, COX-2, and TIMP-1 when compared to vehicle alone in the ligature group (P<0.05). MMP-9 expression and MMP-9/TIMP-1 ratio were similar among rats with ligature-induced periodontitis (P>0.05); however, MMP-9 activity was lower in the group treated with desipramine (P<0.05). Desipramine administration reduced alveolar bone loss as histologically observed, and modulated key bone remodeling and inflammatory mediators in rats with ligature-induced periodontitis.

Antidepressant effects of piperine and its neuroprotective mechanism in rats

To study the antidepressant effects of piperine in chronic unpredictable mild stress (CUMS) rats and to explore the underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis. Fifty rats were housed alone and exposed to an unpredicted sequence of mild stressors to induce CUMS, and then were divided into untreated group, desipramine group and low-, medium- and high-dose piperine groups. Another 10 normal rats were used as normal control. The behavior of the rats was detected by body weight and sucrose preference test, and the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in different groups were observed by radioimmunoassay. The results indicated that after 21-day administration, piperine at concentrations of 10 and 20 mg/kg could significantly improve the behavioral disorder by increasing sucrose consumption. Piperione at concentrations of 5, 10 and 20 mg/kg could remarkably reduce serum ACTH and CRH levels in the CUMS rats, but had little effect on the content of CORT. Piperine can relieve depression in CUMS rats by modulating the function of HPA axis.

Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double‐blind, randomized, placebo‐controlled study

Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short-term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short-term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double-blind, randomized, placebo- controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short-term clinical advantage.

Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg − 1 day − 1 of desipramine, fluoxetine or 10 mg kg − 1 day − 1 of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (− 6.1%, p < 0.01) and tofisopam higher TbTh (+ 5.0%, p < 0.05) versus placebo. Rolipram and tofisopam treatments induced higher BV/TV than placebo (+ 23.8% and + 18.3% respectively). Desipramine group had significantly higher cortical area (+ 4.8%, p < 0.01) and fluoxetine lower cortical area (− 6.1%, p < 0.01) compared to placebo. The stiffness and Young's modulus were lower in the fluoxetine group (77 ± 13 N mm − 1 , 6431 ± 1182 MPa) than in placebo (101 ± 9 N mm − 1 , 8441 ± 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (− 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone.

A Double-Blind, Multicenter, Parallel-Group Study of Paroxetine, Desipramine, or Placebo in Breast Cancer Patients (stages I, II, III, and IV) With Major Depression

This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.

Is clinical response to tricyclic antidepressants in functional bowel disorders related to dosage?

Background: Desipramine (DES) is effective in treating moderate to severe Functional Bowel Disorder (FBD) over Placebo(PLA) as shown in the per protocol analysis of a Randomized, Controlled trial (Drossman at al, Gastroenterology 2003). Clinical experience suggests that benefit from antidepressants in FBD can be achieved at doses lower than those used to treat major depression. However, it is not known if monitoring the DES plasma levels in respect to dose adjustments or predicting clinical outcome in patients with FBD is clinically useful. Aim: To determine whether clinical response to DES is related to DES blood levels or number of pills taken. We report the correlation between DES dose and plasma level, DES dose and chnical outcome and DES plasma level and clinical outcome. Methods: As part of a study of antidepressant and psychological treatments in 431 patients with FBD at UNC or U of Ioronto, we studied those participants in the per protocol analysis taking DES (N = 95, dose 50-150 rag/day) or pill placebo (PLA) (N=55 1-3 pilLs/day). A composite outcome score (Satisfaction with treatment and McGill pain Questionnaires, global Well-being, and IBS-QOL) of clinical response was correlated with: 1)DES plasma levels at week 6 of a 12 week study, and 2) number of pills taken over sequential weekly periods (weeks 0-12,212,4-12,6-12,8-12,10-12) for participants taking DES and PLA. In addition, a correlation was obtained comparing number of DES pills taken with DES plasma levels. Results: 1) There is a correlation between DES blood levels at week 6 and DES dose during weeks 5&6 (R= 0.28, p<0.05); 2) There is no association between DES dose for any sequence of weeks or for DES blood levels at week 6 and the composite score at week 12; 3) These findings held for the DES group after those with non detectable blood levels were excluded; 4) There was no correlation between number of placebo pills taken with the composite score or blood levels (non detectable). Conclusions: For patients with moderate to severe FBD treated with DES, there is a modest correlation between DES dose and plasma level. However, the clinical response is not determined by the DES dose or plasma level. This supports the cresting wisdom that patients with FBD may respond even to low doses (e.g., 50 mg or less) of DES. Monitoring the DES plasma levels in patients with FBD appears not clinically useful unless toxicity is suspected Supported by N1H Grant R01DK49334.

Desipramine restricts estral cycle oscillations in swimming

1. 1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state .

The impact of sertraline, desipramine, and placebo on psychomotor functioning in depression

AbstractImpairment of psychomotor performance is a common adverse effect of many antidepressants, particularly tricyclics. Desipramine is thought to be an exception, with possible performance enhancing effects on psychomotor function. This multicentre study examined the relative effects on psychomotor function of sertraline versus desipramine versus placebo in mild to moderate depression.Fifty‐eight patients who satisfied DSM‐III‐R criteria for major depression and had a minimum HAM‐D score of 15 (17 items) completed eight weeks of treatment. They underwent a standardized assessment which included depression and anxiety rating scales (HAM‐D, HAM‐A, MADRS) and a battery of psychomotor performance tests (The Simple and Choice Reaction Time, The Digit Symbol Substitution and The Trail Making Test), before, during, and after eight weeks of treatment with sertraline, desipramine, or placebo.At baseline, there was a trend for both the sertraline and placebo groups to exhibit better psychomotor performance than desipramine. No significant differences were found between groups after treatment nor between groups for the change from baseline to week 8. However, at week 3, the sertraline group performed significantly better in the trail making test than the placebo patients (p&lt;0.05). Within each treatment group, there was a trend towards improvement in performance for all four parameters from baseline to the end of the study, with these improvements being most obvious in the desipramine group. Sertraline, however, was found to be associated with significantly fewer other adverse effects than the desipramine group, i.e. sweating, dry mouth, anorexia.These results suggest that desipramine and sertraline do not adversely affect psychomotor performance and may even enhance it in mild to moderately depressed patients.

Chronic desipramine alters stress-induced behaviors and regional expression of the immediate early gene, c-fos

This experiment examined the effects of acute or chronic administration of the antidepressant drug desipramine on conditioned stress-induced behaviors and regional c-fos expression in the brain. To this end, rats were exposed to three sequential daily sessions of uncontrollable foot-shock and matched, on the basis of crouching, into one of four groups. Two of these groups were exposed to saline injections twice daily and two were exposed to injections of desipramine (5 mg/kg, SC) twice per day, for 9 days. On the 10th day one of the saline groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Likewise, on the 10th day one of the desipramine groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Detailed behavioral analysis showed that compared to the sajine-treated controls only the group treated chronically with desipramine, including on the test day, exhibited statistically significant reductions in crouching and increases in exploration during the test session. Similarly, Fos immunohistochemistry revealed that the chronic desipramine group showing positive behavioral effects was the only group in which there were significant reductions in the number of stress-induced Fos-positive neurons in five of 60 structures surveyed. These structures included the anterior cingulate cortex, anterior claustrum, central nucleus of the amygdala, dentate gyrus of the dorsal hippocampus, and paraventricular nucleus of the thalamus. To the extent that repeated exposure to uncontrollable stress is an animal model of depression, these and previous results suggest that these structures are potentially important neural targets for the antidepressant effects of desipramine.

Response to Desipramine Treatment in Adolescent Depression: A Fixed-Dose, Placebo-Controlled Trial

To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group (p = .03). Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

Desipramine Treatment for Cocaine Dependence

As a test of the efficacy of desipramine (DMI) in the treatment of cocaine dependence, 59 cocaine-dependent males, maintained on methadone for the treatment of opiate dependence, completed a 12-week, random-assignment, placebo-controlled trial of this medication. At the end of treatment, there were no overall differences between the placebo and DMI groups on a range of outcome measures, including urine toxicology tests. However, an interaction between psychiatric diagnosis and outcome was seen when the sample was divided into those with (51%) and those without (49%) antisocial personality disorder (ASP). Patients with ASP made few gains with either DMI or placebo. Those without ASP made a number of gains with DMI but not placebo, particularly in the areas of psychiatric symptoms, legal status, and family problems. DMI had a significant effect on the psychiatric symptoms and personal adjustment problems, but not the cocaine use, of non-antisocial cocaine abusers. The negative influence of ASP that has been seen in studies of psychosocial therapies for substance-use disorders may also apply to pharmacological therapies.

Chronic desipramine enhances aniphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens

There is accumulating evidence that some antidepressant treatments can increase the functional output of the meso-aecumbens dopanunergic system. For example, chronic administration of tricyclic antidepressant drugs such as imipramme and desipramine (DMI) enhances the locomotor stimulant effects of d-amphetamine Subsensitivity of inhibitory dopamine (DA) autoreceptors and supersensitivity of postsynaptic DA receptor mechanisms are among the mechanisms that have been suggested to underlie these observations. The present experiments investigated the effects of acute and chronic DMI treatment on interstitial DA concentrations in the nucleus accumbens and striatum using in vivo microdialysis in awake freely moving rats (48 h following implantation of a microdialysis probe). Neither acute (5 mg/kg b.i.d. for 2 days followed by 72 h withdrawal) nor chronic (5 mg/kg b.i.d. for 21 days followed by 72 h withdrawal) DMI influenced the ability of apomorphine (25 μtg/kg s.c.) to decrease extracellular concentrations of DA or its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens. In contrast, d-amphetamine (1.5 mg/kg s.c.)-induced increases in extracellular DA were significantly enhanced in the nucleus accumbens of the chronic but not the acute DMI group. This effect was at least partially regionally selective, as significant effects were not observed in the striatum. In accordance with previous reports, the locomotor stimulant effects of d-amphetamine were also enhanced in the chronic DMI groups. DMI itself failed to alter the interstitial concentrations of DA and its metabolites in the nucleus accumbens of the control and chronic DMI groups. These results provide in vivo neurochemical confirmation that chronically administered DMI does not produce DA autoreceptor subsensitivity. They also demonstrate that chronic DMI-induced increases in the locomotor stimulant effects of d-amphetamine are accompanied by a selective potentiation of the effects of this stimulant on interstitial DA concentrations in the nucleus accumbens.

Effects of antidepressants on entrainment of circadian rhythms

Brown Gregory H. and Jo Seggie: Effects of antidepressants on entrainment of circadian rhythms. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1988, 12 :299–306 1. 1. Anti-depressant drugs alter the period of circadian rhythms under free running conditions. We have examined whether treatment with anti-depressants alters such rhythms under conditions of entrainment to a lighting cycle or following a phase advance of the lighting. 2. 2. In the first experiment, following entrainment to a 10L:14D lighting schedule, male Long Evans rats were injected daily for three weeks, with either saline, desipramine or clomipramine at a dose of 10 mg/kg. Under these conditions, the resting circadian patterns of serum corticosterone and melatonin were not affected. 3. 3. In a second experiment, male Wistar rats, adapted to a 12L:12D lighting cycle, were implanted with transmitters, permitting continuous recording of temperature. Animals were given chow supplemented with clomipramine or desipramine so that plasma clomipramine levels were within the normal therapeutic range for humans and desipramine levels were at 4–6 times the therapeutic range. After three weeks of drug treatment, the mean 24 h pattern of temperature was decreased and phase advanced by 72 min in the desipramine group compared to clomipramine or controls. Following a 6 h phase advance in the lighting cycle, the three groups responded differently. The clomipramine group evidenced the most rapid advance in the acrophase, equivalent to 6.9 h, while the saline and desipramine treated groups re-entrained significantly more slowly. 4. 4. Clomipramine, given to achieve clinically meaningful blood levels, does not alter the circadian temperature rhythm under constant conditions of alternating light and dark, but significantly accelerates the rate of re-entrainment to a 6 h phase advance of the lighting schedule.

Alprazolam

The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy.

Effect of lithium upon desipramine enhanced shock-elicited fighting in rats

Rats were tested for changes in shock-elicited fighting (SEF) following the chronic administration of saline (IP); lithium (Li +) (20 mEq./l tap water) + saline (IP); desipramine (DMI) (15 mg/kg, IP); and DMI + Li + for 14 days. The repeated test trials indicated a significant decrease in SEF in Li +-saline group ( p<0.05), a significant increase ( p<p.05) in the DMI group, but no difference in the DMI + Li + group in comparison to saline controls. Combined treatment with DMI + Li + significantly reduced ( p<0.05) SEF in comparison to the DMI group. These results suggest that enhanced aggressivity resulting from chronic DMI administration and measured by SEF can be a useful behavioral model to study the action of lithium.

Functional evidence for subsensitivity of noradrenergic α 2 receptors after chronic desipramine treatment

The effects of acute (2 day) and chronic (15 day) administration of desipramine (DMI) on clonidine-induced suppression of exploratory behavior was investigated in the rat. In accordance with previous results, low doses (25–100 μg/kg) of clonidine produced a dose-dependent decrease in explaratory activity in control animals. This effect of clonidine was markedly attenuated in the chronic DMI groups. Acute treatment with DMI was without effect. The results provide behavioral support for recent biochemical and neurophysiological data which have suggested that chronic DMI administration results in subsensitivity of presynaptic receptors on central noradrenergic neurons.