Nortriptyline for treatment-resistant depression

BACKGROUND: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. METHOD: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. RESULTS: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. CONCLUSION: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.     

A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients.

Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72+/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55% ), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.     

A differential response to nortriptyline and fluoxetine in melancholic depression: the importance of age and gender

OBJECTIVE: To consider the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine in melancholic depression. METHOD: Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender. RESULTS: Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age 18-24 years, especially women, had a markedly superior response to fluoxetine. CONCLUSION: Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.     

Paroxetine versus nortriptyline in the continuation and maintenance treatment of depression in the elderly

Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.     

Antidepressant prescribing in nursing homes: is there a place for tricyclics?

OBJECTIVE: To deduce a model describing physicians' choice of antidepressants for treating elderly nursing home patients. METHODS: Subjects were geriatric residents of 137 skilled nursing facilities who regularly received an antidepressant medication for at least one month (n = 3,440, 28% of all residents). Reasons for prescribing antidepressants and physicians' diagnoses of depression and dementia were identified by medical record audit. Residents were grouped by dementia and antidepressant target symptoms (depression, or one or more non-psychiatric symptoms, i.e. insomnia, pain, incontinence, itching). RESULTS: Selective serotonin reuptake inhibitors (SSRIs) were prescribed preferentially over tricyclic antidepressants (TCAs) for treating depression in both demented and non-demented residents, but TCAs were nine times more likely to be prescribed for treating non-psychiatric target symptoms alone. When non-psychiatric target symptoms were present without depression or dementia, both amitriptyline and nortriptyline prescribing was increased, but amitriptyline appeared to be the antidepressant of choice. In all subgroups examined, its use was two to five times more prevalent when such symptoms were present. In patients with dementia, amitriptyline prescribing declined whether or not non-psychiatric target symptoms were present, but nortriptyline prescribing did not; nortriptyline was three times more likely than amitriptyline to be prescribed in the presence of dementia. CONCLUSIONS: Physicians prescribe anticholinergic TCAs principally to treat common non-depressive symptoms in nursing home residents, preferring SSRIs for uncomplicated depression and depression with dementia. They tend to avoid prescribing anticholinergic TCAs other than nortriptyline when they recognize a patient as demented. The data suggest that physicians employ a decision model for antidepressant prescribing that simultaneously recognizes the utility of TCAs in treating non-psychiatric symptoms and the anticholinergic vulnerability of older, especially demented, patients. Whether or not this model leads to optimal patient management requires further study.     

Heuristic comparison of sertraline with nortriptyline for the treatment of depression in frail elderly patients.

Studies have demonstrated that the selective serotonin reuptake inhibitor antidepressants have similar efficacy to other agents, such as tricyclic antidepressants. However, data are limited for direct comparisons with other antidepressants. The authors conducted a contemporaneous comparison of nursing home residents treated with open-label sertraline in doses up to 100 mg/day with nursing home residents treated in a double-blind randomized study of low vs. regular doses of nortriptyline. There were 97 patients enrolled in the study (28 treated with sertraline), with an average treatment duration of 55 days. There were no differences in the tolerability of sertraline vs. nortriptyline. However, in this group of frail older adults, sertraline was not as effective as nortriptyline for the treatment of depression.     

Use of Antidepressants in Treatment of Comorbid Diabetes Mellitus and Depression as Well as in Diabetic Neuropathy

After a brief review of epidemiology, the focus is on biochemistry of diabetes. Animal and human studies are reviewed in terms of the impact of alterations in catecholamines and serotonin (5-hydroxytryptamine, 5HT) on glucose utilization. Then, the implications of these experimental results for the choice of antidepressant in comorbid diabetes mellitus and depression as well as in diabetic neuropathy are discussed. Results of clinical investigations are then reviewed in terms of the above hypotheses. An Index Medicus Search for the past 10 years was supplemented by references from previous related reviews of the topic as well as by pending results, where available, not previously published. The range of prevalence of depression in diabetic patients has been 8–27%, depending on study criteria and procedures. An increase of catecholamines appears to increase glucose while both reducing insulin release and reducing sensitivity to insulin that is available. In contrast, increases in serotonergic function by increased precursor, increased release, or blocked metabolism and blocked reuptake in contrast seem to increase sensitivity to insulin and reduce plasma glucose. There have been six studies of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), at a dose of 60 mg/day pursued up to 12 months that have demonstrated that medication's usefulness in diabetic patients, with reductions in weight (to 9.3 kg), in FPG (to 45 mg%), and in HbA1c (to 2.5%). In studies in comorbid diabetes mellitus and depression, nortriptyline, a norepinephrine reuptake inhibitor that produces increased synaptic catechols, has led to worsening of indices of glucose control. However, fluoxetine and sertraline, both selective serotonin reuptake inhibitors, in the same patient group, have produced results consistent with reductions in glucose levels. In diabetic neuropathy, perhaps due to the fact that catecholamines and serotonin may both be implicated in pain pathways, dual-action antidepressants appear more effective at lower doses than do specific serotonergic agents. The tricyclic antidepressants (TCA) (66.7%) have had success in double-blind studies, particularly imipramine, with a 81% response rate. Yet, there are positive reports concerning the SSRIs (paroxetine, citalopram, sertraline), as well as nefazodone, that focus on serotonin selectivity. Conclusions: In comorbid diabetes mellitus and depression, most evidence supports the use of fluoxetine in control of glucose handling. Other characteristics in terms dosing, drug interactions, cognition, and sleep make sertraline an attractive alternative agent. In diabetic neuropathy without depression, the best choices among non-TCAs may include sertraline, citalopram, and perhaps, venlafaxine, since the TCAs appear to increase cravings and increase FBG levels.     

Pharmacotherapy for late-life depression

The 2001 expert consensus guidelines for treating major depressive disorder (MDD) in geriatric patients recommended antidepressant treatment in combination with psychotherapy. Recent evidence continues to support the use of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors as first-line agents in the elderly, and although the transdermal monoamine oxidase inhibitor selegilene has shown promise in adult patients, it has not been studied in geriatric depression. Augmentation therapy with atypical antipsychotics or other agents may provide benefits for agitated, psychotic, or resistant MDD in the elderly. The few treatment studies that have been conducted in the geriatric population since the publication of the guidelines have had mixed results and high placebo response rates. More large controlled trials are needed.     

Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit

OBJECTIVE: To determine the prevalence of hyponatraemia associated with selective serotonin reuptake inhibitor (SSRI) and venlafaxine use in elderly patients compared to that in elderly patients not prescribed these drugs, while controlling for age, sex, depression status and illnesses or prescribed medications also associated with hyponatraemia. Design and setting Retrospective controlled analysis in a 36-bed inpatient unit for elderly psychiatric patients in Melbourne. PATIENTS: Inpatients (199) with a mean age of 74.2 years of whom 74 were prescribed an SSRI or venlafaxine. RESULTS: Patients on SSRIs or venlafaxine were 5.6 times as likely as patients not so treated to have hyponatraemia. Thirty-nine percent of patients on an SSRI or venlafaxine had hyponatraemia compared with 10% of controls. Ten of the 14 patients on venlafaxine were hyponatraemic. Controlling for thiazide status did not reduce the odds of these patients having hyponatraemia and taking an SSRI or venlafaxine was still strongly associated with hyponatraemia after also controlling for age, sex, and depression status, consumption of other drugs potentially causative of hyponatraemia and medical illness severity (Odds Ratio (OR) 3.5, p = 0.008). CONCLUSIONS: SSRI and venlafaxine use is strongly associated with the presence of hyponatraemia in a population of elderly psychiatric inpatients and the association is not due to confounding by age, sex, depression status, medical illness severity or consumption of other drugs. Elderly patients on SSRIs or venlfaxine should have sodium levels checked before and after commencement of antidepressant treatment.     

Open-trial maintenance pharmacotherapy in late-life depression: survival analysis

We report preliminary findings from an ongoing, open trial of maintenance nortriptyline pharmacotherapy in 27 elderly depressed patients (median trial length: 18 months). While patients were on maintenance nortriptyline (mean dose: 50 mg/day) with steady-state plasma levels in the range of 50-150 ng/ml, 58% of Q-6 monthly ratings on the Hamilton Rating Scale for Depression have been 10 or lower, Folstein Mini-Mental State ratings have remained above 27, and a minimal level of side effects with no increase over time has been observed. Four of 27 patients (14.8%) have suffered recurrences and have required rehospitalization at 6, 9, 10, and 13 months. Survival analysis showed an 85% survival rate (without recurrence) at 12 months and 81.5% at 18 months. Mean survival time without recurrence is 21.3 months to date. Although our pilot experience with maintenance nortriptyline in late-life depression appears more favorable than outcomes reported in earlier naturalistic studies (where no attempt was made to keep patients in systematic maintenance therapy), the need for controlled studies of maintenance therapies in late-life depression is nonetheless underscored by the current data and other naturalistic data from the United Kingdom.     

Possible therapeutic effect of clonazepam upon elderly depressive patients

The patient, a 77‐year‐old man, was diagnosed with senile depression. He was also diagnosed with depression at other hospitals, and pharmacotherapy by antidepressants was carried out. He was given sulpiride, selective serotonin reuptake inhibitors, a serotonin‐norepinephrine reuptake inhibitor, an atypical antidepressant, and tricyclic and tetracyclic antidepressants, but conventional pharmacotherapies using these antidepressant drugs did not alleviate his symptoms. The patient was then administered 0.5 mg/day of clonazepam at bed time. Following 2 weeks of administration, his symptoms were alleviated. The dosage of clonazepam was increased to 0.75 mg/day and remission was facilitated. Four weeks later, the patient displayed further alleviation of his depressive symptoms, so he has been continued on 0.75 mg/day of clonazepam. Essential drug selections for senile depression includes selective serotonin reuptake inhibitors, serotonin‐norepinephrine reuptake inhibitors, and atypical antidepressants, but when these are ineffective, tricyclic antidepressants or tetracyclic antidepressants are alternatively selected. When a patient’s symptoms are not alleviated by essential drug selection, as occurred in the current case, clonazepam is considered to be another therapeutic candidate. If they fail to alleviate symptoms, however, then early referral to a specialist is crucial. Enhancing primary‐care physicians’ understanding of senile depression and coordination with specialists is essential in the medical care of elderly patients with depression.     

Obsessive compulsive disorder, depression, and fluoxetine

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.     

Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: Clinical description and the role of the 5-HTTLPR

Abstract

Objectives. Sexual dysfunction (SD) is a frequently reported side-effect of antidepressant treatment, particularly of selective serotonin reuptake inhibitors (SSRIs). In the multicentre clinical and pharmacogenetic GENDEP study (Genome-based Therapeutic Drugs for Depression), the effect of the serotonin transporter gene promoter polymorphism 5-HTTLPR on sexual function was investigated during treatment with escitalopram (SSRI) and nortriptyline (tricyclic antidepressant). Methods. A total of 494 subjects with an episode of DSM-IV major depression were randomly assigned to treatment with escitalopram or nortriptyline. Over 12 weeks, depressive symptoms and SD were measured weekly with the Montgomery–Asberg Depression Rating Scale, the Antidepressant Side-Effect Checklist, the UKU Side Effect Rating Scale, and the Sexual Functioning Questionnaire. Results. The incidence of reported SD after 12 weeks of treatment was relatively low, and did not differ significantly between antidepressants (14.9% escitalopram, 19.7% nortriptyline). There was no significant interaction between the 5-HTTLPR and antidepressant on SD. Improvement in depressive symptoms and younger age were both associated with lower SD. The effect of age on SD may have been moderated by the 5-HTTLPR. Conclusions. In GENDEP, rates of reported SD during treatment were lower than those described in previous reports. There was no apparent effect of the 5-HTTLPR on the observed decline in SD.     

Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction

BACKGROUND: Depression after myocardial infarction (MI) is associated with higher morbidity and mortality. Although antidepressants are effective in reducing depression, their use in patients with cardiovascular disease remains controversial. OBJECTIVE: To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study. DESIGN: Observational secondary analysis. SETTING: Eight academic sites. PATIENTS: The Enhancing Recovery in Coronary Heart Disease clinical trial randomized 2481 depressed and/or socially isolated patients from October 1, 1996, to October 31, 1999. Depression was diagnosed using a structured clinical interview. This analysis was conducted on the 1834 patients enrolled with depression (849 women and 985 men). INTERVENTION: Use of antidepressant medication. MAIN OUTCOME MEASURES: Event-free survival was defined as the absence of death or recurrent MI. All-cause mortality was also examined. To relate exposure to antidepressants to subsequent morbidity and mortality, the data were analyzed using a time-dependent covariate model. RESULTS: During a mean follow-up of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR, 0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% CI, 0.32-0.90), compared with patients who did not use selective serotonin reuptake inhibitors. For patients taking non-selective serotonin reuptake inhibitor antidepressants, the comparable HRs (95% CIs) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73 (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent MI, respectively, compared with nonusers. CONCLUSIONS: Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality. A controlled trial is needed to examine this important issue.     

Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older

BACKGROUND: Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. METHODS: Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50-150 mg) or nortriptyline (25-100 mg). RESULTS: Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. CONCLUSION: The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.     

3H-imipramine binding in depressed elderly: relationship to family history and clinical response

Platelet 3H-imipramine binding (Bmax) was determined in 34 elderly (mean age 64.8) unipolar depressed outpatients who were being treated with either nortriptyline or interpersonal psychotherapy for 10 to 16 weeks, and in nondepressed elderly controls. Bmax values were decreased in the depressed group. In addition, Bmax values were depressed further in subjects with a history of depression in first degree relatives. Good clinical response with either nortriptyline or psychotherapy was associated with lower Bmax compared to those subjects who had a poorer response to treatment. Treatment nonresponders and those with a negative family history of depression had Bmax values that were somewhat decreased but not significantly different from controls. This study extends to the elderly the potential applicability of platelet 3H-imipramine binding as a marker of depressive illness, and proposes a predictor for treatment response in elderly unipolar depressed patients.     

Augmentation strategies in geriatric depression

Approximately 30–40% of elderly patients with major depression have inadequate response to an initial therapeutic trial of antidepressant medication. In these cases augmentation of the antidepressant has been recommended as one way of improving the rate of response. This article reviews the literature on augmentation strategies in treatment-resistant geriatric depression. Successful augmentation with lithium, triiodothyronine, stimulants, carbamazepine, valproate and a tricyclic–serotonin reuptake inhibitor combination have been described. However, there have been no controlled trials and, with the exception of two open prospective studies of lithium potentiation, the literature consists entirely of case reports and retrospective case series. As a result, it is difficult to draw conclusions about the efficacy of these strategies in late life, especially since treatment failures seldom get reported. Side-effects may limit the usefulness of some augmentation regimens in old age—up to 25% of patients treated with lithium or carbamazepine discontinued these medications because of adverse events. There is a need for controlled studies to better determine the clinical utility of augmentation strategies in physically well depressed elderly, as well as those with depression complicating medical illness, dementia and other neurological disorders.     

Patterns and predictors of remission,response and recovery in major depression treated with fluoxetine or nortriptyline

OBJECTIVE: The first objective of this paper was to describe the pattern of remission, response and recovery in patients with major depression who were randomised for treatment with fluoxetine ornortriptyline. The second objective was to report on the demographic and diagnostic predictors of the response and recovery in these depressed patients. METHOD: One hundred and ninety-five patients with major depression were recruited for this outpatient study. After a detailed clinical and neurobiological evaluation patients were randomized to receive either fluoxetine or nortiptyline as an initial antidepressant treatment. RESULTS: Of the 195 depressed patients randomised to treatment,154 completed an adequate 6-week trial of either fluoxetine or nortriptyline as their initial antidepressant. Of the 41 patients who did not complete an adequate trial the dropout rate was higher on those randomized to nortriptyline (p = 0.02). There was also an important interaction of drug and gender in determining dropouts in that women did not complete an adequate trial with nortriptyline and men did not complete an adequate trial with fluoxetine (p = 0.002).Of the 154 patients who completed an adequate 6-week antidepressant trial there were no significant differences in 6-week measures of depression severity or of percentage improvement. However, if we use an intention to treat analysis and dichotomise outcomes into response,remission or recovery; then recovery rates were significantly higher with fluoxetine than nortriptyline (p = 0.005).Using an intention to treat analysis fluoxetine was superior tonortriptyline in women, in those less than 25-years old, and in those with atypical depression. Independent of drug, those with chronic depressions had a poorer outcome. CONCLUSION: In this sample of depressed patients randomized tonortriptyline or fluoxetine the change in depressive symptoms over 6 weeks were comparable between fluoxetine and nortriptyline. However,when we look at the more clinically important variable of recovery then fluoxetine was superior to nortriptyline. Predictors of a poorer response to nortriptyline were gender, young age and atypical depression.The results challenge traditional beliefs that selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.     

Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo.

Speed of response is an important clinical issue in the treatment of depressed elderly patients. Our objective was to compare rapid response rates in a study combining therapeutic sleep deprivation (TSD) with paroxetine with two earlier randomized, double-blind studies in late-life depression, one of paroxetine versus nortriptyline and another of nortriptyline versus placebo. We measured depressive symptoms with the 17-item Hamilton Rating Scale of Depression (HRSD), defining rapid response as an HRSD < or = 10 by 2 weeks. With combination therapy (TSD + paroxetine), 9 of 13 patients (69%) experienced a rapid response. In the nortriptyline versus paroxetine study, nortriptyline brought about rapid response in 12 of 37 (32%) and paroxetine in 11 of 43 patients (26%). In the third study, rapid response to nortriptyline occurred in 10 of 41 patients (24%) and to placebo in 6 of 39 patients (15%). The overall chi square, including the rate of rapid response to placebo, was 14.87 (P = .005). The chi square on the four active treatment groups, excluding placebo, was 10.28 (P = .016). This preliminary observation suggests that combined therapy with TSD plus paroxetine may be twice as successful at achieving rapid response in elderly depressed patients than conventional monotherapy with medication or placebo. A prospective, placebo-controlled evaluation of this dual therapy is warranted.     

Should selective serotonin reuptake inhibitors be prescribed to all patients with ischemic heart disease?

Recent studies have uncovered more and more evidence demonstrating the adverse relationship between depression and ischemic heart disease. One of the most significant mechanisms that may explain the adverse relationship is the increased platelet activity, otherwise known as aggregation, observed to occur in patients with depression or ischemic heart disease. Platelet activity is further elevated in patients with depression and ischemic heart disease. Selective serotonin reuptake inhibitors are antidepressants and also act like platelet inhibitors. The results of large-scale clinical trials suggest that the use of selective serotonin reuptake inhibitors may reduce cardiac events in post-myocardial infarction patients or in those with unstable angina that may be related to the effects of selective serotonin reuptake inhibitors on platelet aggregation.