Life cycle and loss--the spiritual vacuum of heroin addiction.

This research studied the function of heroin addiction as a family-learned method of coping with death, separation, and loss across the life cycle. Heroin addicts, psychiatric outpatients, and normal students were given an extensive interview and test battery to determine the incidence of loss of family members and significant others. Because the impact of death is often overcome through religious rituals, this study also investigated the subjects' perception of their families' religious values and orientation to life's meaning and purpose. Results indicate that the incidence of death differs significantly across groups and that addicts have a distinct orientation to death, are more suicidal, and have more premature and bizarre death experiences. During childhood they have more family separations, and they tend to develop a distinct pattern of continuously separating from and returning to their families. They are also less likely to have a clearly defined purpose in life. A subset of parents from each group were also interviewed and tested, and these results support the theory of the intergenerational transmission of behavior.

One-year follow-up of anxious patients treated with diazepam.

A 1-year follow-up was conducted on patients who had participated in a 6-month diazepam maintenance study. Of 180 patients contacted, 131 patients (73%) responded. Observed relapse rate was 63%, and Hopkins Symptom Checklist (HSCL) scores at follow-up were significantly higher for relapsed than for nonrelapsed patients. Two thirds of all relapsed patients sought some kind of medical, social, or psychiatric help, frequently including medication. Patients who were the most improved at the end of the diazepam maintenance trial consistently had the lowest HSCL scores at the time of follow-up. The implication of these findings for the management of chronic anxious patients is discussed.

Early treatment response in anxious outpatients treated with diazepam.

Two hundred and two moderately chronic psychiatric outpatients, all suffering from anxiety of at least moderate severity and all diagnosable as cases of Generalized Anxiety Disorder, participated in a single-blind 6-week trial of diazepam (15-40 mg/day). The trial was preceded by a 1 week placebo washout, and provided for evaluation visits after 1, 2, 4 and 6 weeks of diazepam treatment. Patients were divided into High, Medium and Low Initial Improvers using 1 week change in Hamilton Anxiety Scale total score to assign patients to three subgroups of equal size. These groups did not differ significantly on those demographic factors and attributes of illness history which were documented, nor on assessments of symptom and illness severity, and mode of intake. Examination of a number of patient and physician assessments of illness severity revealed that the High group had the greatest 6-week improvement, the Low group the least. During the first week, the High group attained 86%, the Medium group, 65%, and the Low group, 29% of its full 6-week drug response. Diazepam dose levels were lowest for the High group and highest for the Low group. Placebo response was least for the High group and greatest for the Low group. An attempt to find distinctive attributes of the three initial improvement groups was unsuccessful.

Six-week trial with diazepam: some clinical observations.

Side effects, improvement, and predictors of response were examined in 295 patients treated for greater than or equal to 1 week with diazepam; 234 of these patients completed 6 weeks of treatment. The greatest improvement occurred during the first week of treatment. Sedation was the predominant side effect. Predictors of improvement included low educational level, lack of previous treatment, presence of precipitating stress, low occupational and/or family adjustment, low levels of trait anxiety, and high levels of state anxiety.

Diazepam and desmethyldiazepam plasma concentrations in chronic anxious outpatients.

Within the framework of a large-scale clinical study on the effect of diazepam in chronic anxiety, diazepam (D) and desmethyldiazepam (DD) plasma concentrations were determined frequently. Significant relationships were found between the clinical effect and the plasma concentrations of D and DD, respectively; a curvilinear relationship resulted if the dosage was disregarded, but within the individual dosage groups the relationship was found to be linear. For these computations, the daily diazepam dose was treated as a covariable in a factorial analysis of variance approach. It was found, in addition, that the daily diazepam dose was one of the most significant predictors of the plasma concentration of D or DD, respectively. The steady state plasma concentrations were highest in patients experiencing an exacerbation of their conditions of anxiety if they were returned to placebo after 14 to 22 weeks of diazepam medication. The lowest steady state concentrations were found with those patients who showed withdrawal symptoms under these conditions.

Long-term diazepam therapy and clinical outcome.

This double-blind study involved the continuous (six to 22 weeks) treatment of 180 chronically anxious outpatients with diazepam, 15 to 40 mg/day. Our findings indicate that a significant number of patients benefit from prolonged diazepam treatment and that tolerance to the anxiolytic effect of diazepam does not develop during a 22-week study period. The duration of continual treatment with sedative-benzodiazepines was clearly the most important determinant of withdrawal reactions. Patients treated continuously for less than eight months with sedative-benzodiazepines had an incidence of withdrawal of 5%, whereas 43% of patients treated for eight months or more demonstrated clear withdrawal reactions. While these withdrawal reactions produced considerable distress, they were neither life threatening nor incapacitating and did not include convulsions or psychotic reactions. In all cases, withdrawal reactions could be readily managed by gradually tapering the dose of the benzodiazepine.

Physician prognosis in relationship to drug and placebo response in anxious and depressed psychiatric outpatients.

The relationship between treating physician's prognosis and treatment response to active drug or placebo in samples of 517 anxious and 569 depressed outpatients who had participated in 4-week double-blind drug trials was examined. Log-linear analyses employing diagnosis, prognosis, treatment (active drug or placebo), and treatment response were conducted. Anxious patients had been treated with either chlordiazepoxide or placebo, and depressed patients had received either amitriptyline or placebo. Significant differences were found, suggesting that physician prognosis is related to pharmacologically induced symptom relief in anxious but not in depressed patients. In the depressed patient sample, prognosis and improvement were found to be significantly related in placebo but not drug-treated patients.

The impact of favorable and unfavorable life events on psychotropic drug response.

A group of 410 primarily anxious psychiatric outpatients treated with chlordiazepoxide, 244 treated with diazepam, and 537 receiving placebo were asked to report any significant favorable or unfavorable life events which occurred during both the first and the second 2 weeks of a 4-week double-blind drug trial. The frequency with which favorable and unfavorable events were reported did not differ across medication groups. However, patients reporting unfavorable events showed significantly less improvement after 2 and 4 weeks of treatment than did patients reporting no events or patients reporting favorable events. The amount of improvement experienced by patients reporting positive events did not differ significantly from that of patients reporting no events. The size of the impact of reported events upon outcome did not vary with treatment agents. Essentially similar results were obtained when data based on 2- and 4-week patient improvement ratings were analyzed. It was concluded that the occurrence of significant life events during the course of drug trials of the type involved here did not affect the sensitivity with which drug-placebo differences could be detected.

Coffee consumption, cigarette smoking and reporting of drowsiness in anxious patients treated with benzodiazepines or placebo.

Data obtained from anxious outpatients treated with either chlordiazepoxide or diazepam (n = 533) or placebo (n = 285) were used to explore the impact of coffee/tea and cigarette consumption upon the frequency of reporting of drowsiness after 2 weeks of treatment. Strong evidence was provided that both cigarette smoking and coffee drinking affect the frequency with which drowsiness is reported by patients receiving the two benzodiazepines. However, not only the magnitude but also the direction of the impact of coffee consumption upon drowsiness depends upon the level of cigarette smoking and vice versa. For patients smoking less than or equal to 1 pack of cigarettes/day, drowsiness is reported less frequently by heavy coffee users while for patients smoking greater than 1 pack of cigarettes/day, drowsiness is reported more frequently by heavy coffee users. Similarly, for patients drinking less than or equal to 2 cups of coffee/day, drowsiness occurs less frequently among heavier smokers while for patients drinking greater than 2 cups of coffee/day, drowsiness occurs more frequently among heavier smokers. These results are consistent with reports that particular substances contained in coffee and tea and in cigarette smoke stimulate the synthesis of hepatic enzymes which metabolize both the benzodiazepines here studied and the substances which have stimulated enzyme synthesis.

Nonspecific factors and side effect complaints. Factors affecting the incidence of drowsiness in drug and placebo treated anxious and depressed outpatients.

Discriminant function analyses were applied to data obtained from anxious psychiatric outpatients treated with either chlordiazepoxide (n = 353) or placebo (n = 259) and depressed outpatients treated with either amitriptyline (n = 310) or placebo (n = 328), who had participated in controlled drug trials of 4 weeks' duration, in an attempt to identify factors associated with complaints of drowsiness made by these patients. Although the magnitude of the relationships between individual predictors and drowsiness was small, several factors emerged which had consistent impact across treatment groups. Predictors of complaints of drowsiness attributed to active drugs arose primarily from demographic attributes probably reflective of life style, and from illness and treatment history. In contrast, predictors of drowsiness attributed to placebo were almost exclusively confined to indices of the severity of several aspects of presenting symptomatology. In particular, more frequent complaints of drug-induced drowsiness were found among better educated individuals with an illness of long duration. Complaints of placebo-induced drowsiness were more common among patients with more severe emotional (phobic-obsessive) symptomatology and more frequent headaches and among those individuals in whom hypochondriasis was less severe.

The Minnesota Multiphasic Personality Inventory in predicting response to pharmacotherapy of neurotic outpatients.

The utility of the Minnesota Multiphasic Personality Inventory (MMPI) in predicting treatment response to pharmacotherapy for a group of 54 anxious and 43 depressed outpatients was examined. Discriminant function analyses using the MMPI scales were conducted on groups of improved and unimproved patients. Several significant function, as well as zero-order, differences were found. In general, improved patients scored significantly lower on scales reflecting depression and obsessive-compulsive or schizoid tendencies. They also obtained lower scores on scales measuring interpersonal sensitivity and suggestive of character traits such as low frustration tolerance, impulsivity, and resentment toward authority figures. Additional analyses in which several different profile types were compared for treatment outcome revealed few differences among groups.

Prediction of response to chlordiazepoxide and placebo in anxious outpatients: an attempt at replication.

The present study seeks to determine the extent to which a set of non-specific factors can stably predict response to either chlordiazepoxide (CDZ) or placebo (PBO) and the extent to which such prediction is specific to or distinctive for each treatment agent. For this purpose data were assembled for 447 primarily anxious neurotic outpatients treated with either CDZ or PBO in 4 week double blind drug trials performed over the past ten years and divided into two comparable subsamples for each treatment agent. A series of analyses revealed modest replicability but considerable drug specificity for a Global improvement measure. Replicability was considerable higher for a patient measure of Symptom Change, but its specificity to treatment agent was considerably less.

Diazepam and halazepam in anxiety: some prognostic indicators.

A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians.