Performance characteristics and clinical utility of diagnostic criteria proposals in bereaved treatment-seeking patients.

BACKGROUND: Persistent complex bereavement disorder (PCBD) is a protracted form of grief included in DSM Section 3 indicating a need for more research. Two other criteria sets [prolonged grief disorder (PGD) and complicated grief (CG) disorder] are also currently in use by researchers. This study evaluates rates of diagnosis of each proposed criteria set in a clinical sample of bereaved individuals participating in clinical research. METHOD: Two groups in which persistent grief was judged to be present or absent completed an assessment instrument that included items needed to diagnose PCBD as well as PGD and CG. One group included grief treatment-seeking participants in our multicenter National Institute of Mental Health (NIMH)-sponsored study who scored ⩾30 on the Inventory of Complicated Grief (ICG) and the other comprised bereaved adults enrolled in clinical research studies who scored <20 on the ICG. Rates of diagnosis were determined for proposed PCBD, PGD and CG criteria. RESULTS: PCBD criteria diagnosed 70 [95% confidence interval (CI) 64.2-75.8] % of the grief treatment-seeking group, PGD criteria identified 59.6 (95% CI 53.4-65.8) % of these individuals and CG criteria identified 99.6 (95% CI 98.8-100.0) %. None of the three proposed criteria identified any cases in the bereaved comparison group. CONCLUSIONS: Both proposed DSM-5 criteria for PCBD and criteria for PGD appear to be too restrictive as they failed to identify substantial numbers of treatment-seeking individuals with clinically significant levels of grief-related distress and impairment. Use of CG criteria or a similar algorithm appears to be warranted.

Does early-onset chronic or recurrent major depression impact outcomes with antidepressant medications? A CO-MED trial report.

BACKGROUND: Prior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear. Method A total of 665 psychiatric and primary care out-patients (aged 18-75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks. RESULTS: Early-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correlates (longer duration of illness, greater number of prior episodes, greater likelihood of atypical features, higher rates of suicidality and psychiatric co-morbidity, fewer medical problems, poorer quality of life, greater history of child abuse/neglect). However, results from unadjusted and adjusted analyses showed no significant differences in response, remission, tolerability of medications, quality of life, or retention at 12 or 28 weeks. CONCLUSIONS: Although early-onset chronic/recurrent MDD is associated with a more severe clinical picture, it does not seem to be useful for predicting differential treatment response to antidepressant medication. Clinicians should remain alert to an increased risk of suicidality in this population.

Is prior course of illness relevant to acute or longer-term outcomes in depressed out-patients? A STAR*D report.

BACKGROUND: Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes. METHOD: This cohort study recruited out-patients aged 18-75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n = 398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n = 387). Acute treatment was up to 14 weeks of citalopram (≤ 60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR(16)) ≤ 5] or response (≥ 50% reduction from baseline in QIDS-SR(16)) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ≥ 11]. RESULTS: Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse. CONCLUSIONS: Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.

An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.

Isocarboxazid and placebo were evaluated in 130 anxious depressives. Drug was superior to placebo on depression, anxiety, interpersonal sensitivity, and global measures, and on symptoms of hostility, anxiety, obsessiveness, and psychological-cognitive components of depression. There were no significant differences between treatment effects on psychomotor and typical vegetative symptoms. Isocarboxazid was more effective than placebo in major, but not in minor, depression. It was significantly more effective in depression classified as endogenous depression or melancholia by various diagnostic criteria. Drug was more effective than placebo in atypical depression with vegetative reversal and in Brief Psychiatric Rating Scale (BPRS)-derived profiles of anxious and hostile depression; there were no drug-placebo differences in atypical depression without vegetative reversal, or in BPRS retarded and agitated/excited depression. Interpersonal sensitivity emerged as an important drug-responsive dimension.

Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia.

Neuropathologic and brain imaging studies have produced evidence of brain abnormalities in schizophrenic patients, often within the cerebrum's limbic lobe, and, less frequently, within basal ganglia. In the present study we used magnetic resonance imaging morphometric techniques to estimate volumes of specific cerebral structures in schizophrenic patients and age- and sex-matched normal controls. Estimates of the volume of mesial temporal lobe structures were reduced and estimates of the volume of the lenticular nucleus were increased in the schizophrenic patients. There was also evidence of reduced cranial volume in some schizophrenics. The magnitude of the lenticular abnormality, but not the temporal lobe abnormality, was associated with age at first psychiatric contact; earlier onset was associated with larger lenticular nuclei. The possible relevance of these results to neurodevelopmental hypotheses about the pathogenesis of schizophrenia is discussed.

The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results.

Forty schizophrenic outpatients and 40 normal subjects were assessed using extensive clinical (eg, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms) and neuropsychological (extended Halstead-Reitan Battery) measures. The schizophrenic patients had multiple neuropsychological deficits on tests of complex conceptual reasoning, psychomotor speed, new learning and incidental memory, and both motor and sensory-perceptual abilities. Neuropsychological impairment correlated more strongly with negative than positive symptoms. Overall, the schizophrenic outpatients showed relatively modest increases in the number of perseverative responses on the Wisconsin Card Sorting Test of abstraction flexibility. A subgroup of these schizophrenic patients seemed to be particularly impaired on the Wisconsin Card Sorting Test. This pattern of results, in conjunction with previous studies, supports the idea that, while some schizophrenic patients may have fixed, frontally based dysfunctions, these dysfunctions may be most prominent, and even fixed, in deteriorated, kraepelinian patients. These data provide evidence for diffuse and far-reaching deficits in a majority of outpatients with chronic schizophrenia.

Neuropsychological deficits in schizophrenics. Relationship to age, chronicity, and dementia.

BACKGROUND: We sought to determine whether neuropsychological impairment in schizophrenia is related to current age, age at onset, or duration of illness, and whether the pattern of such impairment can be distinguished from that caused by progressive dementias of Alzheimer's type. We administered a comprehensive neuropsychological test battery to a normal control group (n = 38), a group of ambulatory patients with Alzheimer's disease (n = 42), and three ambulatory schizophrenic groups: early onset-young (n = 85), early onset-old (n = 35), and late onset (n = 22). Tests were grouped and analyzed according to eight major ability areas, and published procedures were used to remove the expected effects of normal aging. RESULTS: The three schizophrenic groups were found to be neuropsychologically similar to one another and different from normal controls and patients with Alzheimer's disease. There were no significant differences among the schizophrenic groups in level or pattern of neuropsychological functioning. Patients with Alzheimer's disease demonstrated less efficient learning and particularly more rapid forgetting than did the other groups. CONCLUSIONS: These findings suggest that neuropsychological impairment in schizophrenia is unrelated to current age, age at onset, or duration of illness. The study further suggests that the encephalopathy associated with schizophrenia is essentially nonprogressive and produces a pattern of deficits that is different from that seen in progressive cortical dementias.

Effects of transdermal clonidine treatment on withdrawal symptoms associated with smoking cessation. A randomized, controlled trial.

In a double-blind, randomized, placebo-controlled trial, we studied 40 cigarette smokers to determine the effects of one week of transdermal clonidine hydrochloride (Catapres-TTS No. 2) treatment on the withdrawal symptoms associated with smoking cessation. Subjects were instructed to maintain their usual cigarette intake during days 1 through 3 and cease smoking for days 4 through 6. All of the withdrawal symptoms measured (craving, irritability, anxiety, restlessness, difficulty concentrating, and hunger) significantly increased during the three days of smoking cessation in the placebo group. There was a 4.3-fold increase in craving, a 3.8-fold increase in irritability, a 3.7-fold increase in anxiety, and a 3.3-fold increase in restlessness in the placebo group compared with the transdermal clonidine group during the three days of smoking cessation. Impairment of concentration and hunger were not significantly diminished by transdermal clonidine treatment during smoking cessation. In addition, a trend was present in the transdermal clonidine group to spontaneously decrease the number of cigarettes smoked per day during the smoking period. Side effects were generally mild. We conclude that transdermal clonidine treatment ameliorates some of the short-term withdrawal symptoms, especially craving, associated with smoking cessation.

Isocarboxazid in the treatment of depression.

Of 50 outpatients with nonpsychotic, nonmelancholic, anxious depression, the 24 patients taking isocarboxazid had better scores on all outcome measures than the 26 patients taking placebo. Differences on several variables reached statistical significance by weeks 4-6.

Depression through the first year after the death of a spouse.

OBJECTIVE: This study assesses the frequency of depressive syndromes during the first 13 months after the death of a spouse. METHOD: Men and women whose spouses had recently died were identified through death certificate records. These subjects completed a multidimensional questionnaire and were interviewed 7-8 weeks (2 months) after the death. Follow-up questionnaires were completed 7 and 13 months after the death. The questionnaires contained specific items corresponding to DSM-III-R criteria for depressive episodes as well as other widely used measures of depressive symptoms such as the Zung Depression Scale and the Hopkins Symptom Checklist. RESULTS: Eighty-four (24%) of 350 widows and widowers met criteria for depressive episodes at 2 months, 72 (23%) of 308 did so at 7 months, and 46 (16%) of 286 did so at 13 months. At each time period, the prevalence was substantially higher than the 4% rate of depressive episodes observed in a comparison group of 126 subjects whose spouses were still living. Widows and widowers most likely to meet criteria for depressive episodes 13 months after the bereavement were younger, had past histories of major depression, were still grieving 2 months after the loss, and met DSM-III-R criteria for depressive episodes 2 and/or 7 months after the death. CONCLUSIONS: Depressive episodes are common after the death of a spouse. Clinicians should maintain a high index of suspicion for the possibility of depression, particularly in young widows and widowers who have a past history of depression or who experience a full depressive syndrome soon after the loss.

Clinical implications of DSM-III diagnoses of alcohol abuse and alcohol dependence.

The authors explored the clinical significance of the DSM-III distinction between alcohol abuse and alcohol dependence by studying 403 male primary alcoholics consecutively admitted to an inpatient alcohol treatment program. On intake, 186 men met criteria for alcohol abuse and 217 met criteria for alcohol dependence. The two groups were virtually identical except that subjects with alcohol dependence took more drinks per drinking day and had more alcohol-related medical problems and past hospitalizations. During a 1-year follow-up, men with alcohol dependence were more likely to have visited a public detoxification facility. The results do not support prognostic implications for the differentiation between alcohol abuse and alcohol dependence in alcoholic inpatients.

Measuring symptoms of grief and bereavement.

As part of an effort to develop an instrument to measure grief, a 58-item questionnaire was completed by 211 subjects who had lost a loved one because of death. The results demonstrated wide individual variations in specific symptoms and in their intensity and duration. Long after the immediate grief period, most bereaved individuals continued to feel upset, empty, or tearful; many experienced anniversary reactions and/or physical symptoms; and some had persistent identification phenomena. Although the acute dysphoria peaked between 1 and 2 years, several grief-related feelings, symptoms, and behaviors continued indefinitely. The relevance of present work and directions for future studies are discussed.

The dexamethasone suppression test in acute grief.

Nineteen recently widowed women and men were given diagnostic interviews, psychometric evaluations, and dexamethasone suppression tests (DSTs). While 58% of the subjects (N = 11) met Research Diagnostic Criteria for depression, only 16% (N = 3) were nonsuppressors on the DST. In this population, nonsuppression was related more to levels of anxiety than to depression.

Past substance abuse and clinical course of schizophrenia.

To evaluate the effects of previous alcohol and drug use on the course and symptoms of schizophrenia, the authors compared 34 patients with schizophrenia who had histories of substance abuse with 17 patients with schizophrenia who were lifelong abstainers. Surprisingly, they did not find that individuals with past histories of abuse were more impaired or had more symptoms.

Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes.

OBJECTIVE: The purpose of this study was to determine the effects of antidepressant pharmacotherapy on mood symptoms and psychosocial outcomes in dysthymia. METHOD: In a multicenter, double-blind, parallel-group trial, 416 patients with a diagnosis of early-onset primary dysthymia (DSM-III-R) of at least 5 years' duration without concurrent major depression were randomly assigned to 12 weeks of acute-phase therapy with sertraline, imipramine, or placebo. The psychosocial outcome measures used in the study were the Global Assessment of Functioning Scale, the Social Adjustment Scale, the Longitudinal Interval Follow-up Evaluation psychosocial ratings, and the Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Sertraline and imipramine were significantly better than placebo in improving psychosocial outcomes as measured by the first three instruments. The Quality of Life Enjoyment and Satisfaction Questionnaire scores demonstrated significant improvements from baseline, and both active treatments produced significantly greater improvements than placebo. Significantly fewer patients discontinued sertraline (6.0%) than discontinued imipramine (18.4%) because of adverse events. CONCLUSIONS: Pharmacotherapy is an effective treatment for dysthymia in terms of psychosocial functioning as well as depressive symptoms, even when the dysthymia is long-standing.

Cross-sectional study of older outpatients with schizophrenia and healthy comparison subjects: no differences in age-related cognitive decline.

OBJECTIVE: Little is known about the progression of cognitive deficits in older, community-dwelling patients with schizophrenia, especially in comparison to healthy subjects. METHOD: The authors examined the relationship of age to performance on the Mattis Dementia Rating Scale in 116 outpatients with schizophrenia and 122 normal comparison subjects. Subjects ranged in age from 40 to 85 years. RESULTS: Dementia Rating Scale scores were lower in the schizophrenia group but correlated negatively with age in both groups, with no significant differences seen between the schizophrenia and normal comparison groups in slopes that depicted age-related variation. CONCLUSIONS: This cross-sectional study suggests a relatively stable long-term course of cognitive impairment in individuals with schizophrenia, with no evidence of faster cognitive decline in outpatients with schizophrenia than in normal comparison subjects.

Depressive symptoms in schizophrenia.

OBJECTIVE: The authors assessed the presence and severity of depressive symptoms, as well as their associations with other clinical measures, in a group of mid- to late-life patients with schizophrenia who were not in a major depressive episode or diagnosed with schizoaffective disorder. METHOD: Sixty outpatients with schizophrenia between the ages of 45 and 79 years and 60 normal comparison subjects without major neuropsychiatric disorders, proportionally matched for age and gender, were studied. Depressive symptoms were rated primarily with the Hamilton Depression Rating Scale. Standardized instruments were also used to measure global psychopathology, positive and negative symptoms, abnormalities of movement, and global cognitive status. RESULTS: Depressive symptoms were more frequent and more severe in schizophrenic patients than in normal comparison subjects; 20% of the women with schizophrenia had a Hamilton depression scale score of 17 or more. Severity of depressive symptoms correlated with that of positive symptoms but not with age, gender, negative symptoms, extrapyramidal symptoms, or neuroleptic dose. CONCLUSIONS: Depressive symptoms are common in older patients with schizophrenia. They may be an independent, core component of the disorder or, alternatively, may be a by-product of severe psychotic symptoms.

Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity.

To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Side effects of isocarboxazid.

Three double-blind, placebo controlled studies found isocarboxazid (40-50 mg/day) to be efficacious and safe for the treatment of atypical depression. The few instances of liver function elevations were generally borderline; one patient had a marked increase of both SGOT and SGPT (with normal bilirubin and alkaline phosphatase) at Week 6 which normalized over the next several months. Another patient had a mild, temporary hypertensive reaction after eating cheese but did not require any treatment alterations. Drops in both systolic and diastolic blood pressures, as well as orthostatic changes, were common but generally mild and well-tolerated. The most frequently noted side effects were dizziness, headache, dry mouth, insomnia, and constipation. Clinical adverse reactions tended to be mild and to respond to dosage decreases. Isocarboxazid appears to be an underutilized and potentially valuable agent for the treatment of depressed patients.

Diagnosis and treatment of depression in late life.

Major depression and dysthymia are common and often disabling disorders in late life. Several features of late-life depression, such as its frequent association with general medical conditions, polypharmacy, cognitive disturbances, and adverse life events, make accurate diagnosis a substantial clinical challenge. Yet, prompt diagnosis is an important component of implementing appropriate treatment strategies. An ideal treatment program integrates patient and family education, focused psychotherapy, and pharmacotherapy. Because of pharmacokinetic and pharmacodynamic changes associated with aging, lower doses of medication and more gradual dose increases than are required in younger adults are needed in the treatment of elderly depressed patients. In addition, medications should be selected that have minimal antihistaminic, anticholinergic, and antiadrenergic effects, minimal cardiovascular risk, and minimal drug-drug interactions. Since depression in late life tends to be at least as chronic and/or recurrent as depression earlier in life, treatment for acute depressive episodes should last at least 6-8 months, and long-term maintenance treatment should be considered in selected individuals.