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Objective: The purpose of this study was to examine the correlates and consequences of two constructs related to affective experience: neuroticism and affective instability. Method: One hundred thirty-two patients were assessed at intake for axis I and II symptoms, general personality traits, and specific impairments, including impairments in interpersonal functioning. The data included responses to structured and semistructured interviews, self-reports of interpersonal problems, and reports of interpersonal problems from significant others. Clinical ratings of axis I and II symptoms and of impairment were made by using the LEAD (i.e., longitudinal, expert, all data) consensus approach. Ninety-one of the 132 patients were reassessed at 12-month follow-up. Results: Neuroticism and affective instability manifested varied concurrent relations, with neuroticism being strongly related to an anxious, avoidant style and affective instability related to more externalizing personality styles. Prospectively, neuroticism predicted later symptoms, occupational impairment, and global dysfunction, whereas affective instability predicted romantic impairment. Conclusions: The findings suggest that neuroticism and affective instability--which are considered core aspects of personality pathology--are related but distinct constructs with unique correlates and different predictive abilities.

Objective: Anxiety disorders are highly prevalent in elderly persons. However, to date, the efficacy of selective serotonin re-uptake inhibitors (SSRIs) for the treatment of anxiety disorders in this age group has not been established. Method: Thirty-four participants age 60 and older with a DSM-IV anxiety disorder (mainly generalized anxiety disorder) and a Hamilton Anxiety Rating Scale score of 17 or higher were randomly assigned under double-blind conditions to either citalopram or placebo. Response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Improvement scale or a 50% reduction in the Hamilton anxiety scale score. Response and side effects with citalopram and placebo were compared by using chi-square tests and linear modeling. Results: Eleven (65%) of the 17 citalopram-treated participants responded by 8 weeks, versus four (24%) of the 17 placebo-treated participants. The most common and problematic side effect in the citalopram group was sedation. Conclusions: The authors believe this to be the first prospective controlled study to test the efficacy of an SSRI in the management of anxiety disorders among the elderly. These results support the efficacy of citalopram in late-life anxiety disorders. They need to be replicated in a larger study group.

Objective: For many years, it has been assumed that medications affect brain chemistry and physiology but not structure. Recent reports suggest that neuroleptic medication changes basal ganglia volume. To explore this possibility, the authors assessed for basal ganglia volume change in individuals who had their basal ganglia structures delineated and measured on magnetic resonance scans at the beginning and end of a 2-year period and who received neuroleptic medication during this time. Method: The basal ganglia volumes of 23 male patients with schizophrenia spectrum disorders were measured from manual traces delineating the caudate and lenticular nucleus on magnetic resonance images at admission and 2 years later. Patients' neuroleptic exposure was calculated over the 2 years by using a dose-year formula. Results: During the 2-year period, mean basal ganglia volume of patients receiving predominantly typical neuroleptics increased, while the opposite was observed for patients receiving mostly atypical neuroleptics. Correlation analysis for the entire group showed a positive relationship between the 2-year exposure to typical neuroleptic medication and change in basal ganglia volume and the reverse for exposure to atypical neuroleptics. Conclusions: In this group, basal ganglia volume increased following exposure to typical neuroleptics and decreased following exposure to atypical neuroleptics.

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.

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 double-blind 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.

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.

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.

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.

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 (median) 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.

There has been considerable discussion in the literature on the differences between criteria for involuntary commitment that are based on dangerousness and criteria based on need for treatment. A number of states have adopted clinical criteria, and other state legislatures are actively considering them. Some libertarians argue that dangerousness is constitutionally required if a person is to undergo the loss of liberty involved in commitment. Citing widely publicized data from the state of Washington, they predict that a return to clinical criteria would result in a deluge of inappropriate commitments. Some clinicians counter that use of clinical criteria would result in selection of a much more appropriate clinical population and point to research indicating that strict observation of the need-for-treatment provisions of the APA model commitment statute would actually decrease the number of commitments. The author examines state hospital admission and census data from eight states that added need-for-treatment criteria to their commitment codes between 1975 and 1990 and argues that the data indicate that there is little reason to believe that such changes would result in the deluge of admissions predicted by the critics.

Almost all antipsychotic drugs (neuroleptics) used to treat schizophrenic patients work by blocking dopamine receptors. Clozapine is a clinically proven antipsychotic that is classified as atypical since it is presumed to work by other mechanisms. Clozapine has been shown to relieve psychotic symptoms among many schizophrenic patients who have not responded well to standard neuroleptic treatment. In order to investigate possible interactions between concentrations of clozapine in the blood and therapeutic response, 20 male and 9 female hospitalized, adult schizophrenic patients who did not improve with standard neuroleptic treatment were given approximately 400 milligrams a day of clozapine for one month. At the onset of the study, clinical evaluations of patients' symptoms were made, followed by weekly assessments. Daily blood-samples were collected and plasma was analyzed with high-performance liquid chromatography. Plasma values of clozapine and its metabolite norclozapine were analyzed statistically so that concentrations could be computed. Patients were classified as responders if they demonstrated quantitative improvements in symptoms. Data analysis revealed that 37.9 of the patients who had not responded to other neuroleptics responded well to clozapine. A significant relationship was shown to exist between clozapine plasma concentration and symptom response. The threshold plasma concentration necessary for symptom improvement was found to be 350 nanograms per milliliter. Sixty-four percent of the patients with concentration levels greater than threshold were responders. Only 22 percent of the patients with concentration levels below threshold demonstrated any symptom reduction. (Consumer Summary produced by Reliance Medical Information, Inc.)

Very little research has been done on multiple personality disorders and until 1980, there existed almost no documentation. Multiple personality disorder refers to the co-existence of two or more distinct personalities within one person, and at least two of these personalities share control of the individual's behavior. A total of 102 patients with multiple personality disorder were described and assessed to determine the features of this condition. The patients studied were from one of four different clinics in Canada and the group consisted of 92 women and 10 men. To assess characteristics of the group, the patients were interviewed and the Dissociative Disorders Interview Schedule was used. The results showed overall comparable scores for all the subjects; a stable and consistent set of features was also observed. A strong correlation was found between multiple personality and a history of physical or sexual abuse, or both. Between 60 and 82 percent of the subjects had been physically abused; between 68 and 90 percent had been sexually abused; and more than 88 percent of the patients had received one or the other form of abuse in childhood. This substantiates the findings of previous studies, which have indicated that multiple personalty disorder is associated with childhood trauma more than any other known psychiatric disorder. Concurrent diagnoses are common, and typically include substance abuse, depression, somatization disorder (physical symptoms without apparent physical disorder), and borderline personality. In the group studied, over 15 somatic symptoms were noted; more than six had Schneiderian symptoms (these included auditory hallucinations, belief that thoughts, feelings or actions are under the control of an outside force, delusions, or hearing one's thoughts aloud); two or more borderline personality features were observed. Over 90 percent of the subjects experienced symptoms of these three disorders. Over 70 percent of the subjects in this study reported that they believed that another person with a different name was inside them. Further clarification of this condition and the implementation of a standardized screening test for multiple personality disorder should make the diagnosis of the condition more common and show the incidence to be higher than previously thought. An appendix with proposed diagnostic criteria for this disorder to be included in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, is provided. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective: This study characterized cognitive functioning in elderly patients with bipolar disorder. Method: The cognitive functioning of 18 euthymic patients with a history of bipolar disorder I or II, ages 60 years and older, was tested with the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale, and the Executive Interview. Cognitive functioning in these subjects was compared with that of an age- and education-matched group of 45 comparison subjects without mood disorders. Results: Approximately half of the bipolar subjects scored one or more standard deviations below the mean of the comparison subjects on the MMSE (N=8, 44%) and the Mattis Dementia Rating Scale total (N=10, 56%). On the Executive Interview, three subjects (17%) scored between one and two standard deviations below the mean of the comparison subjects. Conclusions: A significant proportion of older bipolar subjects exhibited neuropsychological deficits when they were clinically euthymic.

Objective: This study examined the effects of maintenance treatment for late-life depression on social adjustment. The authors hypothesized that elderly patients recovering from depression would have better social adjustment with medication and interpersonal psychotherapy than with medication or psychotherapy alone. Method: Patients aged 60 and older recovering from recurrent major depression were randomly assigned to one of four treatments: nortriptyline and interpersonal psychotherapy, nortriptyline and clinic visits, placebo and psychotherapy, or placebo and clinic visits. The Social Adjustment Scale was administered every 3 months until illness recurrence. Combined treatment was compared to monotherapy on scores over 1 year among patients who remained in recovery (N=49). Results: Patients receiving nortriptyline and interpersonal psychotherapy maintained social adjustment, which declined in those receiving monotherapy. Conclusions: Treatment of late-life depression with nortriptyline and psychotherapy is more likely to maintain social adjustment than treatment with either alone. Combination therapy improves not only duration but quality of wellness.