Effects of antidepressant treatments on platelet tritiated imipramine binding in major depressive disorder

The effects of four antidepressant treatments on platelet tritiated imipramine binding have been studied in 51 hospitalized patients with severe major depressive disorder. There was an increase in maximum binding (Bmax) during the first week of treatment with antidepressants and electroconvulsive therapy, which was further magnified after three weeks' treatment with the serotonin uptake blockers alaproclate and zimeldine hydrochloride, but the Bmax values returned to baseline levels with nortriptyline hydrochloride and electroconvulsive therapy. The equilibrium dissociation affinity constant (Kd) did not change with any of the treatments. On reexamination one or two years after admission to the study, Bmax had not reached control values in clinically recovered, drug-free patients. Low pretreatment Bmax was associated with delusions during illness and with a poor long-term clinical outcome. There was no correlation between binding parameters and monoamine metabolite concentrations in the cerebrospinal fluid, either before or during treatment.     

Fluoxetine in panic disorder

This paper presents the cases of two patients who suffered from panic disorder with agoraphobia and depression. One had been refractory to alprazolam and tricyclics and to behaviour therapy; she had responded to phenelzine, but due to a weight gain of 50 lbs, had discontinued treatment and she relapsed. The second patient, who also suffered from post-traumatic stress disorder, did not respond to alprazolam, imipramine or to phenelzine, but gained weight (33 lbs) on phenelzine. Both patients responded to fluoxetine 80 mg per day without concomitant weight gain.     

Electroconvulsive shock therapy and maximum binding of platelet tritiated imipramine binding in depression

We studied the tritiated imipramine binding values in platelets from 12 hospitalized untreated patients with endogenous depression and found a significant decrease in maximum binding (Bmax) values compared with a control population of the same age and sex. There were no changes in the equilibrium dissociation affinity constant values between the untreated depressives and the control population. After at least six sessions of electroconvulsive therapy and at the time when a significant clinical improvement of depression was confirmed, the Bmax value of tritiated imipramine binding in platelets was slightly increased but was still significantly below that of the control values. However, when six of these patients were reexamined after 12 to 18 months, at a time when they were euthymic, the Bmax of tritiated imipramine binding in platelets was found in the same range as the values of the control population. Our results indicate that clinical improvement precedes the changes in Bmax of tritiated imipramine binding in platelets from depressed patients. The tritiated imipramine binding in platelets is a useful biologic marker in affective disorders. Furthermore, our results suggest that tritiated imipramine binding in platelets may be a state-dependent biologic marker in depression.     

Mirtazapine versus paroxetine in panic disorder: an open study

Introduction

Open studies suggest that mirtazapine has efficacy in panic disorder treatment. We designed an open study that evaluates changes induced by mirtazapine compared with paroxetine in panic disorder.

Methodology

Patients 18–65 years old consecutively referred to a psychiatry liaison service with panic disorder (DSM-IV criteria) were offered either mirtazapine or paroxetine treatment.

Results

There were statistically significant reductions from baseline to week 3 and from week 3 to 8 for mirtazapine and paroxetine groups for: number of panic attacks, Beck Anxiety or Depression Inventory (BAI, BDI) Clinical Global Impresion (CGI) of panic disorder severity and CGI of panic disorder response (these variables were evaluated by the patient, the clinician or a blind evaluator). Responders at week 3 (BAI decrease of 50%) were 83% for the mirtazapine group and 84% for the paroxetine group. Responders at week 8 (number of panic attacks equal to 0) were 77% for the mirtazapine group and 73% for the paroxetine group Statistically significant differences between mirtazapine and paroxetine were found for number of panic attacks at weeks 3 and 8 and BAI at week 3, suggesting a faster response for mirtazapine. Responders at week 8 maintained a no recurrence figure of 95% at follow-up 6 months later. Panic disorder either with or without comorbid depression improved in both groups of treatment.

Discussion

Our study supports the hypothesis that mirtazapine has efficacy in the treatment of panic disorder either with or without comorbid depression.     

A naturalistic study of imipramine in panic disorder and agoraphobia

This naturalistic study examined the treatment response to imipramine of 60 patients who had panic disorder or agoraphobia with panic attacks. Only half of the patients could tolerate the drug, but of those who did, 88% obtained a markedly beneficial clinical effect. An amphetamine-like side effect accounted for most of the dropouts. More than one-half of the responders achieved clinical remission at doses (less than or equal to 100 mg/day) and plasma levels (less than or equal to 150 ng/ml) considered to be subtherapeutic for depression. There appears to be neither a clear threshold for response nor a therapeutic dose range for imipramine in the treatment of panic. Doses should be adjusted individually and increased conservatively.     

Platelet imipramine binding in patients with panic disorder and major familial depression

Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression. Thus, despite previous findings of an overlap between panic and depressive disorders, the present results suggest that the two syndromes may have distinct neurochemical substrates.     

Decreased platelet imipramine binding in Tourette syndrome children with obsessive-compulsive disorder.

[3H]Imipramine binding to blood platelets was assessed in eight untreated Tourette syndrome (TS) children, nine drug-free TS children with obsessive-compulsive disorder (OCD), and nine age-matched and gender-matched control subjects. The density of [3H]imipramine binding sites in TS + OCD patients was significantly lower compared with TS-OCD patients (28%) as well as when compared with controls (31%). This alteration was not accompanied by differences in the affinity of the binding site to the ligand. The decreased density of the platelet serotonin "transporter" might implicate the involvement of the serotonergic system in the pathophysiology of OCD in TS patients, but not in TS per se.     

Platelet [3H]imipramine binding in patients with panic disorder

[3H]imipramine binding to platelets was measured in 17 drug-free panic disorder patients and 14 healthy controls. No difference in Bmax or Kd values was found between the two groups. Patients with a past history of major melancholic depression or severe agoraphobia had similar binding parameters as panic disorder patients without a history of depression or severe agoraphobia.     

Platelet [3H]imipramine binding in generalized anxiety disorder, panic disorder, and agoraphobia with panic attacks

The density of platelet [3H]imipramine binding sites is reported to be decreased in unipolar depression and, hence, is a putative biological marker. There is considerable evidence for a phenomenological and biological relationship of panic disorder with affective disorder. We studied platelet [3H]imipramine binding site density in unmedicated subjects with generalized anxiety disorder (GAD; n = 55), panic disorder (PD) with and without agoraphobia (n = 52), and normal controls (n = 26) in order to determine whether or not patients with panic disorder differed from controls in this biological assay. We found no differences in binding site density (Bmax) or affinity (Kd) among the PD, PD with agoraphobia, GAD, and control groups. Nor did we find a relationship between Bmax or Kd and the severity of depressive symptoms or the presence of a family history of affective disorder. In view of two conflicting prior studies, the use of [3H]imipramine binding in panic disorder remains problematic.     

Comparative study of platelet 3H-paroxetine and 3H-imipramine binding in panic disorder patients and healthy controls.

High affinity 3H-paroxetine and 3H-imipramine binding sites were simultaneously studied in platelets of 29 untreated patients with panic disorder and 12 healthy controls. The maximum number of binding sites (Bmax) was found to be significantly lower in the panic patients compared to the controls using either ligand. No difference in the Kd values between the groups of subjects was found. The disturbance of serotonin neurotransmission in panic disorder--decrease in Bmax values--may be either a consequence or a reason of serotonergic dysfunction.     

Aggression, hyperactivity and platelet imipramine binding.

We measured platelet 3H-imipramine binding parameters in 16 subjects affected by different types of mental deficiency, all characterized by hyperactive and/or aggressive behaviour, and in 16 healthy controls. The patients had a lower maximum binding capacity than the controls, with no difference in Kd, irrespectively of the type of mental disorder. These findings suggest a link between 5-HT disturbances, reflected by reduced imipramine binding sites, and behavioural dyscontrol, expressed as hyperactivity and aggression.     

Differential 3H-imipramine platelet binding in patients with panic disorder and depression

3H-Imipramine (3H-IMI) binding to platelet membranes was measured in 19 patients with agoraphobia with panic attacks, 9 patients with major depression, and 22 healthy subjects. In comparison to healthy subjects, the maximal number of binding sites (Bmax) was significantly decreased in depressed patients but not in panic disorder patients, and the apparent affinity of binding was slightly decreased in depressed patients but not in panic disorder patients. The Bmax and Kd of 3H-IMI platelet binding did not differ between panic disorder patients with and without a history of a major depressive episode. Thus, 3H-IMI platelet binding is clearly different in patients with panic disorder compared to those with an active depression. Because 3H-IMI binding is associated with the serotonin reuptake site in platelet and brain membranes, these findings give further support to abnormalities in serotonergic function in patients with major depression.     

艾司西酞普兰与帕罗西汀治疗惊恐障碍的比较

目的探讨艾司西酞普兰对京恐障碍患者的疗效及不良反应。方法将66例惊恐障碍患者随机分为艾司西酞普兰组和帕罗西汀组,疗程8周,并用汉密顿焦虑量表（HAMA）、汉密顿抑郁量表（HAMD）、抗抑郁药不良反应评定量表（sERS）对患者治疗前后进行评估。结果在治疗的第1周、第2周末艾司西酞普兰组的HAMA分值均低于对照组,而在4、6、8周末,两组患者的HAMA分值差异无统计学意义。在治疗8周末时,艾司西酞普兰组治愈率为64．5％,有效率为90．3％,帕罗西汀组分别为63．3％、90．0％。两组差异无统计学意义。在不良反应方面,两组差异无统计学意义。结论艾司西酞普兰治疗惊恐障碍疗效与帕罗西汀相当,不良反应无明显差异。     

Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia.

OBJECTIVE: This study was designed to assess and compare the differential relapse rates of patients with panic disorder and agoraphobia after discontinuation of acute treatment (6 months) or acute plus maintenance treatment (18 months) with imipramine. METHOD: Sixteen patients with panic disorder and agoraphobia who had shown marked and stable response to 6 months of acute imipramine treatment and a comparable group of 14 patients who had been in remission during an additional year of half-dose imipramine maintenance treatment entered a 3-month, double-blind discontinuation study followed by a 3-month drug-free period. Assessments of the patients were made according to operationalized response/relapse criteria, and plasma drug concentrations were monitored. RESULTS: Survival analysis revealed significantly different cumulative probabilities of continued response 6 months after discontinuation of imipramine treatment between the patients who had received only acute treatment and those who had received acute and maintenance treatment. CONCLUSIONS: The results support the hypothesis that successful imipramine maintenance treatment of patients with panic and agoraphobia can have protective effects against relapse, at least in the first 6 months after the maintenance treatment period.     

A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study.

BACKGROUND: Serotonin Selective Re-uptake Inhibitors (SSRIs) are the drugs of choice for treating panic disorder (PD). In vitro studies have shown different pharmacodynamic profiles for SSRIs, but their clinical relevance is still unknown. Paroxetine, the SSRI with the strongest serotonergic effect, also shows significant cholinergic and noradrenergic activities. In this class of drugs, citalopram is the most selective for serotonin. We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course. METHOD: Fifty-eight patients with PD were randomly assigned to either the paroxetine or the citalopram treatment group in a single-blind, randomized design. Each patient was assessed at days 0, 7 and 60 by the Panic Associated Symptoms Scale (PASS), the Sheehan Disability Scale (SDS) and the Fear Questionnaire (FQ). Primary outcome measures were the percentage of patients free of panic attacks, anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders, as defined by a reduction of at least 50% from baseline of both PASS and SDS global scores at day 60. RESULTS: At day 60, 86% of patients receiving citalopram and 84% of those receiving paroxetine responded well to treatment. No significant differences between the two drugs were found. Both were well tolerated, although sexual side effects and weight gain were frequent. Anticipatory anxiety decreased significantly after the first week of treatment, and no initial worsening in the panic attacks was observed. CONCLUSION: Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile. Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs.     

Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder

OBJECTIVE: To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder. METHOD: Outpatients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were randomized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline, in daily doses of 50 to 100 mg, or imipramine, in daily doses of 100 to 200 mg. Primary outcome measures were panic attack frequency (derived from patient diaries) and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: 138 patients were treated with sertraline (76% female; mean age = 40 years) and 69 with imipramine (70% female; mean age = 40 years). The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs. Endpoint improvement with sertraline versus imipramine, respectively, on the MADRS was 11.1 +/- 10.8 versus 11.2 +/- 10.4, and on the Clinical Global Impressions-Improvement scale (CGI-I) was 2.1 +/- 1.3 versus 2.4 +/- 1.6. Among study completers, CGI-I responder rates were 88% with sertraline and 91% with imipramine. Treatment outcome was concordant for both diagnoses in approximately 70% of patients and discordant in approximately 30%. Overall, sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events (11% vs. 22%; chi(2) = 4.39, df = 1, p =.04). CONCLUSION: Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder, with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine.