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.     

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.     

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.     

Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease.

OBJECTIVE: This study compared the efficacy, tolerability, and safety of paroxetine and nortriptyline in depressed patients with ischemic heart disease. METHOD: After a 2-week, single-blind placebo lead-in phase, 81 outpatients with DSM-III-R-defined nonpsychotic unipolar major depression and ischemic heart disease were randomly assigned to double-blind treatment with paroxetine or nortriptyline for 6 weeks. Paroxetine was administered at a fixed-flexible dose of 20-30 mg/day. Nortriptyline dose was adjusted with the use of blood-level monitoring to reach a plasma concentration of 50-150 ng/ml. RESULTS: Twenty-seven of the 41 patients who started treatment with paroxetine and 29 of the 40 patients who started treatment with nortriptyline had an improvement of at least 50% in their Hamilton Depression Rating Scale scores. Significantly more patients taking nortriptyline discontinued treatment prematurely (35% versus 10%), and more patients taking nortriptyline had adverse events resulting in termination (25% versus 5%). CONCLUSIONS: Both treatments were efficacious. Sixty-three percent of all patients improved at least 50%, and of these, 90% met the criteria for remission. Paroxetine was better tolerated than nortriptyline and less likely to produce cardiovascular side effects.     

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.     

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.     

Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized,double-blind clinical trial with nortriptyline and paroxetine

Cognitive dysfunction is common in older persons suffering from a major depression. However, the degree to which this dysfunction is reversible with successful treatment of the depression remains uncertain. The present study examined the effects that treatment (randomized double-blind design) with either an SSRI (paroxetine) or a tricyclic antidepressant (nortriptyline) had on cognition in older depressed patients. The patients' performance was compared to that of a group of normal controls of similar age and education. Patients and controls were administered measures of working memory, information-processing speed, episodic memory and attention five times over the course of a 12 week trial. At baseline, the patients performed more poorly than the elderly controls on all cognitive measures. While the patients' performance did improve over the course of their treatment, the magnitude of this improvement did not exceed that produced in the elderly controls by practice alone. The same pattern of results was evident in both intent-to-treat and responder analyses. Thus, there was no evidence that the depressed patients' cognitive performance normalized after response to antidepressant therapy. Neither the patients' age at onset nor their baseline level of cognitive functioning influenced the amount by which their performance improved over the 12 week trial. There was no difference between paroxetine and nortriptyline in the amount of cognitive change associated with treatment. The present results suggest that cognitive dysfunction persists in older depressed patients even after their mood disorder has responded to antidepressant medications.     

Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures.

BACKGROUND: Studies have linked depression to sudden death and serious cardiovascular events in patients with preexisting cardiac illness. Recent studies have shown decreased vagal function in cardiac patients with depression and depressed patients without cardiac illness. METHODS: We compared 20-hour, sleeping, and awake heart period variability measures using spectral analysis, fractal dimension, and symbolic dynamics in two patient groups with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of paroxetine or nortriptyline treatment. RESULTS: Spectral measures showed decreases in awake and sleeping total power (TP: 0.0-0.5 Hz), ultra low frequency power (ULF: 0-0.0033 Hz), very low frequency power (VLF: 0.0033-0.04 Hz), and low-frequency power (LF: 0.04-0.15 Hz) for nortriptyline condition and a decrease in high-frequency power (HF: 0.15-0.5 Hz) for the awake condition in patients who received nortriptyline. A measure of nonlinear complexity, WC-100, significantly increased after paroxetine during the awake condition. CONCLUSIONS: These findings suggest that nortriptyline has stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Paroxetine may have some cardio-protective effects, especially in cardiac patients.     

Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate

Depression is associated with increased cardiovascular mortality in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate variability (HRV) or heart period variability has been linked to sudden death in patients with cardiac disease as well as in normal controls. Recent studies have shown decreased vagal function in cardiac patients with depression as well as in depressed patients without cardiac illness. In this study, we compared 20 h awake and sleep heart period nonlinear measures using quantification of nonlinearity and chaos in two groups of patients with major depression and ischemic heart disease (mean age 59-60 years) before and after 6 weeks of treatment with paroxetine or nortriptyline. Patients received paroxetine, 20-30 mg/day or nortriptyline targeted to 190-570 nmol/l for 6 weeks. For HRV analysis, 24 patients were included in the paroxetine treatment study and 20 patients in the nortriptyline study who had at least 20000 s of awake data. The ages of these groups were 60.4 +/- 10.5 years for paroxetine and 60.8 +/- 13.4 years for nortriptyline. There was a significant decrease in the largest Lyapunov exponent (LLE) after treatment with nortriptyline but not paroxetine. There were also significant decreases in nonlinearity scores on S(netPR) and S(netGS) after nortriptyline, which may be due to a decrease in cardiac vagal modulation of HRV. S(netGS) and awake LLE were the most significant variables that contributed to the discrimination of postparoxetine and postnortriptyline groups even with the inclusion of time and frequency domain measures. These findings suggest that nortriptyline decreases the measures of chaos probably through its stronger vagolytic effects on cardiac autonomic function compared with paroxetine, which is in agreement with previous clinical and preclinical reports. Nortriptyline was also associated with a significant decrease in nonlinearity scores, which may be due to anticholinergic and/or sympatholytic effects. As depression is associated with a strong risk factor for cardiovascular mortality, one should be careful about using any drug that adversely affects cardiac vagal function.     

Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs.

BACKGROUND: The significant morbidity and mortality associated with severe depression and its psychotic or melancholic subtypes necessitate effective and well-tolerated therapy. This review evaluates antidepressant treatments for patients with severe depression. DATA SOURCES: Comparative clinical trials conducted on patients with severe depression were found by an English-language MEDLINE search (1985 to present). Additional studies were identified in article bibliographies. Search terms included depressive disorders, depression and severe, hospitalized, melancholic or melancholia, psychotic, and endogenous. STUDY FINDINGS: Evidence for efficacy of SSRIs in severe or melancholic depression comes from a small but growing number of controlled studies with adequate samples, as well as meta-analyses and retrospective subgroup analysis of premarketing trials. In studies that defined response as a 50% or greater reduction in Hamilton Rating Scale for Depression (HAM-D) scores, response rates ranged from 53% to 64% for SSRIs and 43% to 70% for TCAs. In separate trials on severe depression, venlafaxine and mirtazapine were both more effective than placebo and an active comparator. Nefazodone and bupropion were each found to be more effective than placebo in studies of severe depression. Venlafaxine and mirtazapine have been found to be more effective than fluoxetine. CONCLUSION: SSRIs and TCAs are comparably effective for the treatment of severe or melancholic depression. SSRIs and other newer agents appear to be better tolerated than TCAs, specifically lacking adverse anticholinergic and cardiovascular effects that may limit the use of TCAs. Emerging data with venlafaxine and mirtazapine in severely depressed patients with or without melancholia support the efficacy of these treatments. Nefazodone and bupropion were found to be effective in hospitalized depressed patients. Electroconvulsive therapy (ECT) or combined antidepressant therapy may be useful in some patients with severe depression. Patients with severe psychotic depression may respond better to an antipsychotic-antidepressant combination.     

From the Bench to the Trench: A Comparison of Sertraline Treatment of Major Depression in Clinical and Research Patient Samples

BACKGROUND: New medications that enter the marketplace have been tested almost exclusively in controlled clinical trials conducted in specialty research settings. There is some concern that these carefully selected patient samples may not provide information generalizable to the "real world" clinical population. The purpose of this investigation was to compare results from a large, open-label study of sertraline in the treatment of major depression in the clinical practice setting with pooled results from 2 multicenter, double-blind, placebo-controlled studies conducted in specialty research settings. METHOD: Clinical practice patients (N = 1482), aged 21 to 65 years, from 228 psychiatric clinical practice sites across the United States participated in the open-label treatment study (Clinical Practice sample). Patients who met DSM-III-R criteria for moderate-to-severe unipolar major depression (i.e., had pretreatment Hamilton Rating Scale for Depression [HAM-D] scores >/= 18) were treated for 8 weeks with sertraline in a flexible dosing fashion (50-200 mg daily). Outcomes on the HAM-D and Clinical Global Impressions-Improvement scale (CGI-I) were compared with the pooled results from 2 previously published placebo-controlled, multicenter treatment studies of sertraline in outpatients with major depression (N = 280). The overall response to sertraline in the Clinical Practice sample was compared with the outcome from the research study patient sample (Clinical Research sample). Additionally, comparison of outcomes of patients with common depressive subtypes (double depression, anxious depression, and melancholic ["endogenous"] depression) were examined. RESULTS: The percentage of sertraline-treated patients rated as responders on the CGI-I was significantly higher in the Clinical Practice sample compared with the Clinical Research sample (87% vs. 73%; p <.001). Sertraline was also much better tolerated in the Clinical Practice sample than in the Clinical Research sample as evidenced by significantly lower overall reports of adverse events (9.4% vs. 13.2%; p <.05) and lower patient dropout rates (17.5% vs. 34.3%; p <.01). Among clinical practice patients, sertraline was found to be equally effective in treating endogenous/melancholic and anxious subtypes and only mildly less effective in achieving a response in patients with double depression (chronic low-grade depression with a superimposed major depression). A regression analysis identified older age and double depression as being predictors of a slower time to response. More than 70% of patients who reported nonresponse to previous treatment with fluoxetine or a tricyclic antidepressant responded to sertraline. CONCLUSION: The effectiveness and tolerability of sertraline treatment was found to be significantly better in the Clinical Practice sample, suggesting that the results from controlled studies in research settings may represent an underestimate of the benefits of a drug. More effectiveness research is needed to confirm and extend these findings.     

Executive functioning, illness course, and relapse/recurrence in continuation and maintenance treatment of late-life depression: is there a relationship?

OBJECTIVE: The authors tested the hypothesis that impaired executive functioning leads to high rates of relapse and recurrence in late-life depression. METHODS: They analyzed data from subjects participating in two independent intervention trials. Study I included 53 elderly depressed patients who participated in an open trial comparing the efficacy of paroxetine and nortriptyline and recurrence prevention over 18 months. Study II focused on 146 elderly depressed patients who received open treatment with paroxetine in a relapse-prevention study over 4 months of continuation treatment. They examined the effect of cognitive functioning, in general, and executive functioning, in particular, on time-to-relapse/recurrence, using baseline and post-treatment measures of neuropsychological functioning. RESULTS: The associations between cognitive measures and both probability of, and time-to-relapse/recurrence were small and statistically nonsignificant. CONCLUSION: Data failed to support the hypothesis that cognitive impairment, in general, or executive dysfunction, in particular, predicts relapse or recurrence of major depression in late life. Authors recommend future testing of the hypothesis with detailed, comprehensive measures over longer periods of observation during maintenance trials.     

Efficacy of controlled-release paroxetine in the treatment of late-life depression

BACKGROUND: Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition. METHOD: In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score. RESULTS: The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo. CONCLUSION: Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.     

DSM melancholic features are unreliable predictors of ECT response: a CORE publication

OBJECTIVE: To determine the relationship between baseline melancholic features with outcomes in patients with major depressive disorder referred for electroconvulsive therapy (ECT). METHOD: In a multihospital (Consortium for Research in ECT) collaborative ECT study, SCID-1 interviews were obtained at study entry. Ratings of the 24-item Hamilton Rating Scale for Depression were obtained thrice weekly during the course of ECT, once during a subsequent treatment-free week, and periodically during 6-month continuation treatment with either bitemporal ECT or nortriptyline plus lithium (continuation pharmacotherapy). RESULTS: The evaluable sample was severely ill with a mean 24-item Hamilton Rating Scale for Depression score of 35.2 (+/-6.9). Of 489 patients, 63.6% (311) met DSM-IV criteria for melancholic features. During acute ECT, 62.1% of those with melancholic features remitted, as compared with 78.7% for those without melancholic features (P = 0.002). During medication continuation treatment (continuation pharmacotherapy), relapse rates were higher for those with melancholic features than for those without these features. Conversely, with continuation ECT, the rate of relapse was lower for those with, compared with those without, melancholic features. CONCLUSIONS: Ascertaining melancholic features by SCID-1 criteria does not identify depressed patients more likely to respond to ECT as had been anticipated from the literature. Melancholic features were associated with poorer treatment outcomes in acute ECT. Those with melancholic features were less likely to relapse with continuation ECT, but those with melancholic features were more likely to relapse with continuation pharmacotherapy. The limitations of the DSM-IV criteria for melancholia are discussed.     

Melancholic/endogenous depression and response to somatic treatment and placebo.

OBJECTIVE: The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. METHOD: Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. RESULTS: Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. CONCLUSIONS: Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.     

A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice.

OBJECTIVE: This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice. METHODS: In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks. RESULTS: More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038). CONCLUSIONS: Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.     

Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy

OBJECTIVE: Few data are available concerning the utility of augmentation in late-life depression treatment. The authors examined likelihood, speed, and predictors of recovery in older adults receiving augmentation pharmacotherapy after inadequate response to standardized treatment with paroxetine plus interpersonal psychotherapy. METHOD: Depression levels were monitored during open treatment in 195 adults age 70 or older. Patients were grouped by whether they required augmentation (bupropion, nortriptyline, or lithium) and compared on likelihood, time, and predictors of recovery. RESULTS: Augmentation was required for 105 patients (53.8%) because of inadequate treatment response (N=77) or response followed by relapse (N=28). Of these patients, 69 received augmentation and 36 did not (primarily because of consent withdrawal or comorbid medical conditions). Patients receiving augmentation showed lower recovery rates than patients never requiring augmentation: recovery occurred in 50.0% of patients receiving it because of inadequate response, 66.7% of those receiving it after early relapse, and 86.7% of patients never requiring augmentation. Patients receiving augmentation because of inadequate response recovered more slowly, with modestly more side effects than other patients. Greater medical burden and anxiety predicted slower recovery. CONCLUSIONS: Despite a lower likelihood of recovery in elderly people receiving augmentation, the recovery by over one-half of such patients suggests the value of augmentation for those able to tolerate it. Need for augmentation presages slower recovery in patients showing initial inadequate response; those requiring it after early relapse recovered more quickly. Strategies to further improve the likelihood and speed of recovery after initial treatment failure are needed.     

Previous mood state predicts response and switch rates in patients with bipolar depression

OBJECTIVE: The treatment of bipolar depression is a significant clinical problem that remains understudied. The role for antidepressant (AD) agents vs. mood stabilizers has been particularly problematic to ascertain. METHOD: Detailed life charting data from 42 patients with 67 depressive episodes were reviewed. Response rates and rates of switch into mania were compared based on the preceding mood state and on whether an AD or mood stabilizing (MS) agent was added following onset of depression. RESULTS: Patients who became depressed following a period of euthymia were more likely to respond to treatment (62.5%) than patients who became depressed following a period of mania or hypomania (27.9%). The ratio of response to switch for previously euthymic patients was particularly favorable. CONCLUSION: Mood state prior to onset of depression in bipolar disorder appears to be an important clinical variable that may guide both choice of treatment administered and expectation of outcome to treatment.     

Social inequalities in response to antidepressant treatment in older adults

CONTEXT: We examined the relationship between socioeconomic status and response to treatment for depression among older adults. METHODS: Secondary analysis of pooled data from the open-label phase of 2 National Institute of Mental Health-funded clinical trials of nortriptyline hydrochloride or paroxetine combined with interpersonal psychotherapy (N = 248). We used Cox proportional hazards regression analyses to examine the association between socioeconomic status, indexed by census tract median annual household income and the subject's educational attainment, and treatment response and remission according to the Hamilton Depression Rating Scale. The association between socioeconomic status and suicidality or depressed mood reported at each week of treatment was examined using repeated-measures generalized logit models. RESULTS: Subjects residing in middle-income census tracts were significantly more likely to respond to antidepressant treatment than subjects residing in low-income census tracts (adjusted hazard ratio, 1.80; 95% confidence interval [CI], 1.18-2.75]). Throughout the course of antidepressant treatment, subjects in the middle- and high-income census tracts were significantly less likely to report suicidal ideation (adjusted odds ratios, 0.48 [95% CI, 0.27-0.94] and 0.39 [95% CI, 0.16-0.94], respectively). No association was found between socioeconomic status and remission. CONCLUSION: Residence in a low-income census tract is associated with a less favorable course of depression among older adults receiving a combination of pharmacologic and psychosocial treatment.     

Melancholia and axis II comorbidity

This study assessed whether the rates of comorbid personality disorders differed between DSM-IV melancholic and nonmelancholic major depressive disorder. We evaluated 260 consecutive depressed outpatients (140 women [53.8%]; mean age, 39.01 +/- 10.4 years) with DSM-III-R major depressive disorder (MDD). MDD was diagnosed with the use of the Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P); enrolled patients were required to have a score >/= 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The presence of the melancholic subtype of major depression was determined with the use of a DSM-IV checklist, while the presence of personality disorders was assessed using the Structured Clinical Interview for DSM-III-R-Personality Disorders (SCID-II). Of the 102 (39.2%) patients who met criteria for melancholic depression and the 158 (60.7%) who did not, there were no significant differences in age, gender, or rates of personality disorder diagnoses. We observed no significant difference in rates of individual personality disorder clusters between melancholic and nonmelancholic depressed patients. Our findings of comparable rates of comorbid personality disorders between melancholic and nonmelancholic depression are consistent with the decision made by the DSM-IV task force to drop the DSM-III-R melancholic feature criterion of "no significant personality disturbance before first major depressive episode" as they challenge the usefulness of trying to establish such absence of premorbid personality features in acutely depressed patients.