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PubMed1994

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.

Age Factors↗
PubMed1996

Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders.

OBJECTIVE: Major depression occurs with generalized anxiety disorder and panic disorder in up to 60% of psychiatric and primary care patients. This comorbidity has been associated with greater severity of depression, poorer psychosocial functioning, and poorer treatment outcomes in psychiatric samples. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder. METHOD: A total of 157 primary care patients who met criteria for major depression were randomly assigned to standardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression, psychosocial functioning, and health-related functioning. RESULTS: Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone. Both standardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder, although time to recovery was longer for the former. Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy. CONCLUSIONS: Standardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder. However, the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention.

Adolescent↗
PubMed1996

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.

Age Factors↗
PubMed1998

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.

Academic Medical Centers↗
PubMedDate not supplied

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.

Age of Onset↗
PubMed2000

Development of major depression after treatment for smoking cessation.

OBJECTIVE: Case studies suggest cigarette abstinence may precipitate a major depressive episode. This study examined the incidence and predictors of major depression in the 12 months after treatment for smoking cessation. METHOD: Participants (N=304, 172 women) were recruited from two trials of smoking cessation. Both trials provided psychological group intervention, but one group received treatment with nicotine gum and the other was given nortriptyline or placebo. The incidence of major depressive episodes was identified by the Inventory to Diagnose Depression, which was administered at follow-up assessments. RESULTS: The 12-month incidence of major depression after treatment for smoking cessation was 14.1% (N=43). Multiple logistic regression analyses indicated that history of depression, baseline Beck Depression Inventory score, college education, and age at smoking initiation were significant predictors of major depression after treatment. Abstinence at the end of treatment did not significantly predict major depression. CONCLUSIONS: Patients who achieved abstinence from smoking showed a risk of developing depressive episodes similar to those who failed to achieve abstinence. As expected, patients who had a history of depression were more likely to experience depressive episodes after treatment for smoking cessation. The 12-month incidence of major depression in this study group was higher than that observed in the general population, but reasons for the elevation were not clear.

Adult↗
PubMed2001

Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder.

OBJECTIVE: The authors' goal was to conduct an adult follow-up of subjects who had participated in a study of nortriptyline for childhood depression. METHOD: The study group represented 100 (90. 9%) of the original 110 subjects and included 72 subjects who had a prepubertal diagnosis of major depressive disorder and 28 normal comparison subjects. Subjects were assessed with semistructured research interviews given by research nurses who were blind to the subjects' original diagnoses. RESULTS: In the original study, the mean age of the children with prepubertal major depressive disorder was 10.3 years (SD=1.5); at adult follow-up the mean age of these subjects was 20.7 years (SD=2.0). At follow-up, significantly more of the subjects who had prepubertal diagnoses of major depressive disorder (N=24 [33.3%]) than normal comparison subjects (none) had bipolar I disorder. Subjects who had prepubertal diagnoses of major depressive disorder also had significantly higher rates of any bipolar disorder than normal subjects (48.6% [N=35] versus 7.1% [N=2]), major depressive disorder (36.1% [N=26] versus 14.3% [N=4]), substance use disorders (30.6% [N=22] versus 10.7% [N=3]), and suicidality (22.2% [N=16] versus 3.6% [N=1]). Parental and grandparental mania predicted bipolar I disorder outcomes. CONCLUSIONS: High rates of switching to mania have implications for the treatment of depressed children. The authors discuss the reasons for their finding a higher rate of bipolar disorder in this outcome study than was found in the one other adult outcome study of prepubertal major depressive disorder.

Adolescent↗
PubMed2001

Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis.

OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.

Adult↗
PubMed1994

Prevention of recurrent postpartum major depression.

OBJECTIVE: Postpartum depression affects between 10 and 15 percent of new mothers. These mothers are apprehensive about recurrence after later births. This study tested the efficacy of antidepressant medication administered during the postpartum period to prevent a recurrence of postpartum depression among women who had suffered a previous episode. METHODS: An open clinical trial was conducted at a university-based outpatient clinic treating pregnant and postpartum women with mood disorders. Study participants were 23 pregnant women who had at least one previous postpartum episode that fit DSM-III-R criteria for nonbipolar major depression without psychotic features. Postpartum monitoring for recurrence of depressive symptoms was compared with postpartum monitoring plus postbirth treatment with either the medication that had been effective for the previous episode or nortriptyline. The first dose was given within 24 hours of birth. The authors assessed recurrence of postpartum major depression by psychiatric examination and use of the Inventory to Diagnose Depression, a reliable self-report instrument. RESULTS: A significantly greater proportion of the women who elected monitoring alone (62.5 percent) suffered recurrence of major depression compared with the women who received monitoring plus medication (6.7 percent) (p = .0086). CONCLUSIONS: Prophylactic antidepressant treatment reduced the recurrence of postpartum major depression.

Antidepressive Agents↗
PubMed1997

Psychiatrists' responses to failure of maintenance therapy with antidepressants.

Some patients being treated for recurrent major depression experience a return of depressive symptoms despite a constant maintenance dose of an antidepressant, a phenomenon known as breakthrough depression. A total of 145 psychiatrists who were members of the Massachusetts Psychiatric Society responded to a survey about intervention in hypothetical cases of breakthrough depression if the patient was taking either 20 mg of fluoxetine, 100 mg of sertraline, 100 mg of nortriptyline, or 40 mg of fluoxetine. For all drugs and dosages, the most popular choice was increasing the dosage, followed by augmenting with lithium or another antidepressant or changing to a different drug.

1-Naphthylamine↗
PubMedDate not supplied

Antidepressant treatment of pathologic laughing or crying in elderly stroke patients.

Pathologic laughing or crying (PLC), a complication of many neurologic disorders, involves behavior that is either inappropriate to the context or to the patient's subjective feeling state. It is due to a dysregulation of the motoric components of emotional experience. PLC is distinct from, but often associated with, major depression. The relatively few reports on treatment of PLC are primarily with tricyclic antidepressants. We report the effective treatment of PLC due to stroke in three patients with nortriptyline or fluoxetine. The cases also illustrate the broad spectrum of depressive symptoms (from none to a major depression) seen in patients with PLC. We discuss treatment implications and directions for future research.

Aged↗
PubMed1976

A comparison of amitriptyline and a fluphenazine/nortriptyline preparation in anxiety-depressive states.

Patients suffering from mixed anxiety/depressive reactions, referred to the out-patient department of a large psychiatric hospital, were treated with either amitriptyline tablets or fluphenazine with nortriptyline (f/n) tablets for a period of four weeks. The study utilized a double-blind, completely randomised design, and patients' progress was assessed by means of the Wing Present State Examination, the Wakefield Self-Assessment Depression Inventory, and a side effects inventory. Both the symptom rating scales showed that purely depressive symptomatology improved significantly in each treatment group, but the patients' self-ratings showed that only f/n produced a significant alleviation of anxiety symptoms and panic attacks. The patients receiving f/n rated themselves as significantly (p less than 0.05) less irritable, as well as less anxious, after 4 weeks treatment, than those receiving amitriptyline. The PSE schedule did not differentiate between the 2 treatment groups, but self-rating, which is a more sensitive method of eliciting drug effectiveness in patients suffering from mild psychiatric disorders, did demonstrate patient preference for f/n. This should have important implications for compliance with treatment.

Adolescent↗
PubMedDate not supplied

Association of antidepressants and other medications with mortality in the residential-care elderly.

To explore the extent to which treatment of depression affects survival, we evaluated the association between use of antidepressant medications and death rates among the residents of a large residential-care facility for the elderly using a retrospective record-review study (N = 624). One year survival, among those taking antidepressants (10.9%), was 11.8% compared to 11.1% among the remainder of the population. A second study followed a group of 32 patients in the same institution who had participated in a therapeutic trial of nortriptyline treatment for major depression. Patients who experienced adverse medical events during treatment exhibited significantly increased mortality; among treatment completers, there was no significant relationship between mortality and therapeutic response. These findings suggest that the inability to tolerate treatment with an antidepressant can be considered a manifestation of physiologic frailty and increased vulnerability to mortality from disease. The previously reported decrease in survival among residential-care patients with major depression is not paralleled by a similar effect in those taking antidepressants. This may reflect selection factors with respect to the ability to tolerate antidepressants, rather an effect of treatment.

Aged↗
PubMed1984

Resin haemoperfusion in levomepromazine poisoning: evaluation of effect on plasma drug and metabolite levels.

Plasma levels of levomepromazine and two of its major metabolites N-desmethyl-levomepromazine and levomepromazine sulphoxide were studied in two poisoned patients treated with resin haemoperfusion at a constant blood flow of 200 ml/min. The mean haemoperfusion clearance of levomepromazine, N-desmethyl-levomepromazine and levomepromazine sulphoxide was 114, 123 and 151 ml/min, respectively, in patient no. 1, and 153, 148 and 184 ml/min, respectively, in patient no. 2. Patient no. 2 had also ingested amitriptyline, and the mean haemoperfusion clearance of amitriptyline and its metabolite nortriptyline was 183 and 183 ml/min respectively. Haemoperfusion did not seem to alter the elimination profile of levomepromazine or the two metabolites in either patient. We conclude that haemoperfusion is of little value in removing levomepromazine, N-desmethyl-levomepromazine or levomepromazine sulphoxide from the body. This is probably due to the large apparent volume of distribution and the high intrinsic hepatic metabolic clearance of these compounds.

Adult↗
PubMed1990

Toxicological findings after fatal amitriptyline self-poisoning.

A case of fatal self-poisoning with amitriptyline is reported. Both the drug and its metabolite nortriptyline were quantified in several post-mortem tissues and fluids, including vitreous humor. Results are discussed in the light of the existing literature.

Adult↗
PubMed1976

A test of the concept of "underlying depressive illness" in the treatment of anxiety states.

In order to test the validity of the concept of anxiety states masking an underlying depressive illness, patients clinically diagnosed as suffering from anxiety or tension states were treated on a random double-blind basis for 4 weeks with either a pure anxiolytic, lorazepam, or an anxiolytic/antidepressant preparation, fluphenazine with nortriptyline. Patients' self-ratings were very similar to the physicians' ratings which showed that fluphenazine/nortriptyline was associated with significantly greater overall improvement(p less than 0.01), as well as significantly greater improvements in the group of symptoms specifically related to depression(p less than 0.05). These results suggest that a depressive element is present in an appreciable proportion of patients presenting with apparent anxiety states, and antidepressant as well as anxiolytic treatment is required. Patients selected on the basis that they had improved satisfactorily at the end of the 4-weeks' treatment were followed up for a further 3 months without medication, and the relapse rate was 24%, irrespective of previous treatment. More of the patients treated with lorazepam had to be excluded from the follow-up because of failure to improve, and these probably represented the proportion (19%) of this population with an appreciable depressive element to their illness.

Adjustment Disorders↗
PubMed1976

Once daily administration of a fluphenazine/nortriptyline preparation in the treatment of mixed anxiety/depressive states.

A study of 223 patients diagnosed as suffering from mixed anxiety/depressive states was carried out in general practice to compare the effectiveness of treatment with a once-daily tablet preparation containing 1.5 mg fluphenazine plus 30 mg nortriptyline, taken either at night or in the morning, with the same total daily dose taken as 1 tablet t.d.s. Patients were randomly assigned to 4-week's treatment with one of the three drug schemes, and patients' self-ratings as well as physicians's ratings were used to assess symptoms. Both rating assessments showed that there were highly significant improvements in each of the three treatment groups over the 4-week period. Although there were no clinically important differences between improvements in the night-time dose and t.d.s. groups, there was a higher incidence of drowsiness and tablet defaulting among patients taking the single morning dose.

Adjustment Disorders↗
PubMed1990

Treatment of depressed in-patients. Cognitive therapy plus medication, relaxation plus medication, and medication alone.

Thirty in-patients received one of three treatments - medication (nortriptyline) alone (MA), relaxation therapy plus medication (RT&M), or cognitive therapy plus medication (CT&M) (each n = 10) - along with ward milieu. The relaxation and cognitive therapy groups participated in 12 therapy sessions. Symptoms of depression and related cognitive variables were assessed at sessions 1, 6 and 12, and at discharge. All groups improved over the course of the study. CT&M and RT&M groups reported significantly fewer depressive symptoms and negative cognitions at discharge than the MA group. The number of subjects judged depressed at discharge was lower in the CT&M group than in the MA and RT&M groups. It is proposed that a consistent rationale for treatment is a significant facilitating factor in achieving behavioural and cognitive changes in depression.

Adult↗