Interpersonal psychotherapy for late-life depression: past, present, and future.

Interpersonal psychotherapy (IPT) has demonstrated efficacy in protecting against a recurrence of major depression in elderly subjects when used alone on a monthly basis and when combined with antidepressant medication. The authors summarize their experience using IPT over the past 10 years and discuss a variety of treatment correlates. In addition, preliminary results using IPT combined with paroxetine in depressed elders reveals no difference in remission rates between cognitively intact and cognitively impaired depressed elders.

A double-blind, placebo-controlled assessment of nortriptyline's side-effects during 3-year maintenance treatment in elderly patients with recurrent major depression.

The authors assessed the severity of nortriptyline's side-effects in older patients with recurrent major depression during placebo-controlled, double-blind maintenance therapy. Data were from 37 patients completing 2-3 years of maintenance therapy; 29 were on nortriptyline and eight were on placebo. The authors detected a time-by-treatment interaction for dry mouth (greater in nortriptyline-treated patients), but no increased association of nortriptyline with constipation, weight change or orthostatic symptoms. Heart rate was consistently higher in nortriptyline-maintained patients as compared with placebo. The total 'side-effect' score on the Asberg Rating Scale, as well as complaints of physical tiredness, daytime sleepiness and nocturnal sleep disturbance, were related primarily to residual depression rather than treatment with nortriptyline.

Which elderly depressed patients remain well on maintenance interpersonal psychotherapy alone?: report from the Pittsburgh study of maintenance therapies in late-life depression.

The aim of this study was to identify elderly depressed patients who can remain well on maintenance Interpersonal Psychotherapy (IPT) alone, after discontinuation of antidepressant medication. Using Cox proportional hazards models, increased severity of depression at pretreatment was associated with increased recurrence rates, to an extent greater in patients maintained on monthly IPT than in those maintained on nortriptyline. The long-term response to maintenance IPT was correctly identified in 20/25 cases by a pretreatment Hamilton score of > or = 20. Fourteen of sixteen patients with pretreatment scores of > or = 20 experienced recurrence of major depression on maintenance IPT, while 6/9 patients with pretreatment scores of less than 20 did not. (Fisher exact P = .01). The same pattern of recurrence in relation to severity was not evident in maintenance placebo, nortriptyline, or combination treatment. In addition, Hamilton scores during continuation treatment were lower (< or = 7) among those who remained well on maintenance IPT than among those who had recurrences. Elderly patients whose depressions are milder at baseline and who show excellent symptomatic remission during acute and continuation therapy may be good candidates for monthly maintenance IPT after initial successful treatment with antidepressant medication and psychotherapy.

Three-year outcomes of maintenance nortriptyline treatment in late-life depression: a study of two fixed plasma levels.

OBJECTIVE: This study compared the long-term efficacy of two fixed plasma levels of nortriptyline in preventing or delaying recurrence of major depression in elderly patients and in minimizing residual depressive symptoms and somatic complaints. METHOD: The authors randomly assigned 41 elderly patients with histories of recurrent major depression to 3-year, double-blind maintenance pharmacotherapy using nortriptyline, with controlled plasma concentrations of 80-120 ng/ml versus 40-60 ng/ml. The authors compared times to, and rates of, recurrence of major depression. They also compared frequencies of side effects, noncompliance episodes, and subsyndromal symptomatic flare-ups. RESULTS: Major depressive episodes recurred for six (29%) of 21 subjects in the 80-120-ng/ml condition and eight (40%) of 20 subjects in the 40-60-ng/ml condition, a nonsignificant difference. Most recurrences took place in the first year of maintenance treatment. Hamilton depression scores in the subsyndromal range (higher than either 10 or 7) occurred significantly more often at 40-60 ng/ml, while constipation occurred significantly more often at 80-120 ng/ml. The proportions of patients reporting missed doses did not differ. CONCLUSIONS: Maintenance pharmacotherapy with nortriptyline at 80-120 ng/ml is associated with fewer residual depressive symptoms, that is, a less variable long-term response, than pharmacotherapy at 40-60 ng/ml, but constipation is more frequent and there is no difference in recurrence of syndromal major depressive episodes. Treatment at 80-120 ng/ml may be preferable, because of fewer residual symptoms and less variability of response, as long as side effect burden can be managed successfully.

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.

CONTEXT: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability. OBJECTIVE: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years. DESIGN: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist. SETTING: University-based psychiatric research clinic. PATIENTS: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions. INTERVENTIONS: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22). MAIN OUTCOME MEASURE: Recurrence of major depressive episode. RESULTS: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years. CONCLUSION: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

How common is resistance to treatment in recurrent, nonpsychotic geriatric depression?

OBJECTIVE: Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly. METHOD: Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy. RESULTS: Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment. CONCLUSIONS: The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.

Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients.

OBJECTIVE: The goal of this study was to examine treatment outcome differences in relation to age at onset of first lifetime episode of recurrent major depression in elderly patients. METHOD: Patients were grouped as having early-onset (N = 129) or late-onset (N = 58) depression. Early onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late onset was defined as age 60 or later. The two groups of patients were compared with respect to demographic and clinical characteristics, types of treatment given (nortriptyline and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did not differ in the percentage of patients who remitted, recovered, or relapsed during continuation treatment or in the percentage who experienced a recurrence of major depression during the first year of maintenance treatment. However, early-onset patients took 5-6 weeks longer to achieve remission than did late-onset patients, and a higher proportion had a history of suicide attempts. CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major depression does not influence short- or long-term treatment response in elderly patients treated with combined interpersonal psychotherapy and nortriptyline, with the exception of slowing the speed of remission in early-onset cases. Difference in remission speed may reflect the greater number of previous episodes in the early-onset patients. Nevertheless, the likelihood of a longer time to remission, together with a higher rate of past suicide attempts, suggests that elderly depressed patients with a history of early-onset illness need particularly careful management.

Which elderly patients with remitted depression remain well with continued interpersonal psychotherapy after discontinuation of antidepressant medication?

OBJECTIVE: This study was conducted to identify which elderly patients with remitted recurrent major depression remain well with maintenance interpersonal psychotherapy after discontinuation of active antidepressant medication (nortriptyline). METHOD: The authors examined outcomes of maintenance therapy over 1 year for 47 elderly patients who were randomly assigned to monthly maintenance interpersonal psychotherapy with placebo (N = 19) or to placebo and a supportive medication clinic without interpersonal psychotherapy (N = 28). A Kaplan-Meier survival analysis was performed on the basis of treatment assignment and subjective sleep quality assessed by the Pittsburgh Sleep Quality Index, on which good subjective sleep quality is indicated by a score of 5 or lower. RESULTS: Nine (90%) of 10 patients reporting good subjective sleep quality (by 1 month into continuation treatment) remained well for at least 1 year when treated with monthly maintenance interpersonal psychotherapy, versus five (31%) of 16 patients with good sleep quality assigned to a medication clinic, three (33%) of nine patients with impaired sleep quality treated with maintenance interpersonal psychotherapy, and two (17%) of 12 patients with impaired sleep quality assigned to a medication clinic. CONCLUSIONS: Recovery of good subjective sleep quality by early continuation treatment is useful in identifying which remitted elderly depressed patients will remain well with monthly maintenance interpersonal psychotherapy, following discontinuation of antidepressant medication, and which patients may be more vulnerable to recurrence of major depressive episodes in the absence of antidepressant medication.

Which depressed patients will respond to interpersonal psychotherapy? The role of abnormal EEG sleep profiles.

OBJECTIVE: The authors tested the hypothesis that patients whose episodes of major depression evidenced more neurobiological disturbance would be less responsive to psychotherapy. METHOD: The study subjects were outpatients who were given a diagnosis of recurrent major depressive disorder (unipolar or bipolar II), according to the Research Diagnostic Criteria, following an interview with the Schedule for Affective Disorders and Schizophrenia. They were classified into a group with normal sleep profiles (N = 50) and a group with abnormal sleep profiles (N = 41) on the basis of a validated index score derived from three EEG sleep variables monitored for 2 nights: sleep efficiency, REM latency, and REM density. The groups' responses to short-term interpersonal psychotherapy were compared by means of chi-square tests and life table and random effects model analyses. Responses to the addition of pharmacotherapy for subjects who did not respond to interpersonal psychotherapy were also compared. RESULTS: The patients with abnormal sleep profiles had significantly poorer clinical outcomes with respect to symptom ratings, attrition rates, and remission rates than the patients with more normal sleep profiles. Seventy-five percent of the patients who did not respond to interpersonal psychotherapy had remissions during subsequent pharmacotherapy. CONCLUSIONS: These findings help to define further a neurobiological "boundary" that may limit response to psychotherapy in depression. An abnormal sleep profile may reflect a more marked disturbance of CNS arousal that warrants pharmacotherapy.

Using interpersonal psychotherapy (IPT) in a combined psychotherapy/medication research protocol with depressed elders. A descriptive report with case vignettes.

One hundred eighty subjects at least 60 years of age with recurrent unipolar major depression were recruited to participate in a depression treatment protocol. All patients received drug therapy with nortriptyline (NT) and interpersonal psychotherapy (IPT) with an experienced clinician. Acutely, 81% of subjects showed a full response to combined treatment. In the initial 127 subjects, the most common problem areas in therapy were role transition (41%), interpersonal disputes (34.5%), and grief (23%). Case vignettes are presented and discussed. The combination of IPT and NT showed a powerful antidepressant effect. IPT was readily adaptable to the needs of depressed elders.

High relapse rate after discontinuation of adjunctive medication for elderly patients with recurrent major depression.

OBJECTIVE: The authors documented outcomes of elderly depressed patients requiring adjunctive medication during acute-phase pharmacotherapy because of slow or partial response to nortriptyline. Twenty-eight patients (17.7%) received inpatient care at some point during acute-phase treatment. METHOD: Rates of response, relapse, and sustained remission were examined in 158 elderly patients with recurrent major depression, grouped by whether they received brief treatment with adjunctive medication (lithium, perphenazine, or paroxetine) (N = 39) or did not (N = 119). RESULTS: The group receiving adjunctive medication had a lower rate of response to acute therapy (64.1% versus 83.2%), a higher relapse rate during continuation therapy (52.0% versus 6.1%), and a lower rate of sustained remission (recovery) (48.7% versus 76.5%) than did the group without augmentation. CONCLUSIONS: Elderly depressed patients requiring augmented pharmacotherapy to achieve remission may need continuation of adjunctive medication to remain well and to avoid early relapse. Alternatively, factors that lead to augmentation in the first place (e.g., heightened anxiety) may also increase the risk of relapse.

Treatment of consecutive episodes of major depression in the elderly.

OBJECTIVE: The purpose of this study was to determine treatment outcome in elderly patients with consecutively treated episodes of recurrent unipolar major depression. METHOD: Subjects were 32 "young" elderly patients with recurrent unipolar depression (mean age = 66.8 years, SD = 5.1) and with two consecutively treated episodes of major depression. Both index and subsequent episodes of major depression were treated in open trial with combined nortriptyline and interpersonal psychotherapy. Rates of remission in index and subsequent episodes were compared by using nonparametric statistics and survival analysis with proportional hazards modeling. RESULTS: Of 30 patients who completed treatment of the subsequent episode, 27 (90%) achieved stable remission of symptoms in both consecutively treated episodes, whereas three patients (10%) did not. Twenty-two (81%) of 27 patients who responded to treatment had a shorter time to remission in treatment of the subsequent episode than in the index episode. Survival analysis with proportional hazards modeling detected a significant difference in time to remission of the index and subsequent episodes (32 paired observations). CONCLUSIONS: In this research study group, recurrent episodes of unipolar major depression in the young elderly were successfully treated to remission in over 80% of patients by using combined pharmacotherapy and psychotherapy similar to that employed in treatment of the index episode. Remission rate and time to remission in consecutively treated episodes were comparable to those in a group of midlife patients with recurrent depression reported by Kupfer et al. in 1989. Thus, recurrent depressive disorder appears to be as treatable in the young elderly as it is in midlife patients.

Applying interpersonal psychotherapy to bereavement-related depression following loss of a spouse in late life.

The efficacy of interpersonal psychotherapy (IPT) as a treatment for outpatients with major depression has been documented in several controlled trials. Recently, IPT has been adapted specifically for depression in late life. The authors report on their experience in applying IPT to geriatric patients whose depression is temporally linked to the loss of their spouses. Detailed treatment techniques are illustrated with case vignettes. Preliminary treatment outcomes are presented for 6 subjects who showed a mean change on the 17-item Hamilton Rating Scale for Depression from 18.5 ± 2.3 SD to 7.2 ± 4.6 after an average of 17 weekly IPT sessions. IPT appears to be an effective short-term treatment for bereavement-related depression in elderly subjects.

Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression.

Recent evidence points to the prophylactic efficacy of maintaining recurrent unipolar patients on the same dose of antidepressant medication that was used to treat the acute episode (Frank et al., 1990; Kupfer et al., 1992). Therefore, the question of whether such patients should be tapered to a lower maintenance dose after successful resolution of an acute episode is clearly important. In this report we describe a small randomized clinical trial in which patients were assigned to either full-dose or half-dose maintenance treatment for a period of 3 years. Survival analysis suggests that superior prophylaxis can be achieved with a full-dose as compared to a half-dose maintenance treatment strategy (p < 0.07). Mean survival time for the full-dose subjects was 135.17 (SE 19.75) weeks as compared to 74.94 (SE 19.78) weeks (median of 43.1 weeks) for the half-dose subjects. We conclude that for patients who have suffered several recurrences, full-dose maintenance treatment is the more effective prophylactic strategy.

Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report.

OBJECTIVE: The authors examined the rate of response to the combination of nortriptyline and interpersonal psychotherapy for acute and continuation treatment of elderly patients with recurrent major depression. METHOD: The subjects were 73 elderly patients, 61 of whom completed treatment. Nortriptyline steady-state blood levels were maintained at 80-120 ng/ml, and interpersonal psychotherapy was administered weekly for 9.1 weeks (medium) of acute therapy and was decreased from biweekly to triweekly during 16 weeks of continuation therapy. During acute treatment nonresponding patients also received brief adjunctive pharmacotherapy with lithium or perphenazine. RESULTS: Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11-14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed. CONCLUSIONS: Use of nortriptyline plus interpersonal psychotherapy for 9.1 weeks (median) of acute and 16 weeks of continuation therapy appears to be associated with good response and relatively low attrition but about a 25% chance of relapse during double-blind discontinuation of nortriptyline. These data require confirmation in a controlled clinical trial of acute and continuation therapy.

Five-year outcome for maintenance therapies in recurrent depression.

After conducting a randomized, 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy, we asked those individuals who survived the 3-year trial receiving active medication (with or without psychotherapy) to continue in a 2-year additional randomized trial of active medication vs placebo. The question was whether maintaining antidepressant medication at the dosage used to treat the acute episode beyond 3 years would continue to provide a significant prophylactic effect compared with medication discontinuation after the 3 years of effective maintenance treatment. Survival analysis demonstrated a highly significant continued prophylactic effect for active imipramine hydrochloride treatment maintained at an average dose of 200 mg. We conclude that active imipramine treatment is an effective means of preventing recurrence beyond 3 years and that patients with previous episodes less than 2 1/2 years apart, therefore, merit continued prophylaxis for at least 5 years.

Efficacy of interpersonal psychotherapy as a maintenance treatment of recurrent depression. Contributing factors.

In earlier reports, we demonstrated that in patients with recurrent unipolar depression, survival time without a new episode of major depression following discontinuation of medication was significantly and positively related to continued interpersonal psychotherapy (IPT). To determine whether the prophylactic benefit of monthly sessions of IPT was a function of specific features of the intervention, we examined the contribution of the quality of IPT sessions to the length of the well interval in this 3-year maintenance trial. Therapy sessions were rated on specificity and purity of interpersonal interventions. Analysis of these ratings indicated that psychotherapy that was more specifically interpersonal was associated with significantly increased survival time. Patients whose therapy sessions were rated above the median on specificity of IPT had a median survival time of almost 2 years, while those below the median had a median survival time of less than 5 months. We concluded that when patient and therapist are able to maintain a high level of interpersonal focus, monthly sessions of IPT have substantial prophylactic benefit.

Three-year outcomes for maintenance therapies in recurrent depression.

We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication.