A controlled trial of adinazolam versus desipramine in geriatric depression

Thirty outpatients between the ages of 60 and 85 with DSM-III Major Depression entered an 8 week randomized, double-blind comparison of desipramine and adinazolam mesylate, a triazolobenzodiazepine derivative. Outcome was assessed on several measures including the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Rating Scale, Clinical Global Impressions (CGI), the 35-item Self-Rating Symptom Scale, and Carroll Depression Scale. Patients in both groups demonstrated a highly significant decrease in average HDRS scores (p less than 0.001) over the course of the study. Adinazolam was associated with significantly greater reduction in average HDRS scores by the third day. Repeated measures analysis of variance showed a significantly greater reduction in HDRS scores for adinazolam over the course of the study. The study medications were associated with distinct patterns of adverse reactions. Desipramine more often produced dry mouth, constipation and nervousness, while adinazolam was more likely to cause drowsiness and lightheadedness. Three of these elderly patients, all of whom were taking desipramine reported at least one fall during the study. Adinazolam may be a promising agent in the treatment of depression in the elderly.     

Intramuscular testosterone supplementation to selective serotonin reuptake inhibitor in treatment-resistant depressed men: randomized placebo-controlled clinical trial

BACKGROUND: Treatment-resistant depression is a persistent clinical problem. Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement, although this strategy has received limited systematic study. OBJECTIVE: The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression. METHOD: Twenty-six healthy adult men with major depressive disorder, partial or nonresponse to 2 adequate antidepressant trials during the current episode, and currently using a selective serotonin reuptake inhibitor were randomized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo, in addition to their existing selective serotonin reuptake inhibitor regimen, for 6 weeks. The main outcome measure was the Hamilton Rating Scale for Depression score. RESULTS: The mean age was 46.4 +/- 10.8 years; mean total testosterone level, 417.5 +/- 197 ng/dL; mean baseline Hamilton Rating Scale for Depression score, 22.2 +/- 5.2; and median duration of the current depressive episode, 6.3 +/- 10.6 years. Hamilton Rating Scale for Depression scores decreased significantly in both testosterone (8.4) and placebo (7.4) groups. Antidepressant response, defined as a 50% decline in Hamilton Rating Scale for Depression score, was achieved by 53.8% (7/13) in the testosterone group and 23.1% (3/13) in the placebo group (P = 0.226). CONCLUSION: Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression.     

Pharmacotherapy improves treatment outcome in depressed cocaine addicts.

Depression is the most common psychiatric disorder in substance abusers, and results in a poorer prognosis and response to traditional chemical dependence and mental health treatment approaches. This article focuses on the use of pharmacotherapy in the treatment of the cocaine addict with secondary depression and provides general clinical treatment guidelines. It also reports on a study in which depressed, methadone-maintained cocaine addicts were treated in a 12-week placebo-controlled trial that compared two pharmacological agents. Patients were randomly assigned to receive placebo, amantadine (a dopamine agonist) or desipramine (a tricyclic antidepressant). The effects of pharmacotherapy were assessed on program retention, cocaine craving, cocaine usage, and depressed mood. Compared to the placebo-treated patients, it was found that the medication-treated depressed patients had a dramatic decrease in their reported cocaine usage (84% versus 17%) and cocaine craving (48% decrease versus 29% increase). Also, the medication-treated depressed patients dramatically increased the percentage of cocaine-free urines compared to the placebo-treated depressed patients who actually decreased their percentage of cocaine-free urines. A measure of depressive symptoms (Beck Depression Index score) increased 100% for the placebo-treated depressed patients, yet remained stable for the medication-treated depressed patients.     

Alpidem and lorazepam in the treatment of patients with anxiety disorders: Comparison of efficacy and rebound

Alpidem, a novel imidazo-pyridine anxiolytic, was compared with lorazepam for efficacy and withdrawal effects in 23 (17 male) anxious psychiatric out-patients of mean age 35.3 years with a mean Hamilton Anxiety Rating Scale (HAM-A) total score of 26.4. Treatment was double blind for 4 weeks with doses built up to a mean of 112.5 mg alpidem and 3.5 mg lorazepam per day. Assessment were made for a further 2 weeks after abrupt withdrawal. There were no differences in scores between the groups before treatment. The HAM-A, Hospital Anxiety and Depression Scale, Sleep Rating Scale and other measures showed both drugs to be equally effective for psychic and somatic anxiety, depression and insomnia. Despite the small numbers, lorazepam produced greater improvement in the anxious mood, fear and insomnia items of the HAM-A. After stopping treatment serious rebound in mood and somatic scores was experienced by the lorazepam group in contrast to those patients on alpidem who maintained their improvement. Neither group was troubled by side effects; dropouts were few and due to inefficacy (1 alpidem) or withdrawal problems (2 lorazepam). Alpidem seemed to offer effective anxiolysis without the risk of rebound associated with lorazepam use.     

A pilot trial of gepirone vs. placebo in the treatment of cocaine dependency.

An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (greater than 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addiction Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI.     

The convergent validity of the Drug Impairment Rating Scale for Cocaine.

The Halikas-Crosby Drug Impairment Rating Scale for Cocaine (HAL DIRS-C) is designed to measure improvement in drug treatment through interval assessment of impact of cocaine use on daily functioning, relationships with other people, other alcohol and drug use, cocaine withdrawal symptoms, adverse effects associated with cocaine use, and personal outlook over the previous week. The scale is a 25-item clinical rating scale administered in the context of a semistructured interview (modeled after and similar to the Hamilton Rating Scale for Depression). The HAL DIRS-C was administered weekly to 147 subjects participating in a 12-week, double-blind medication trial with a psychosocial treatment component. Without breaking the pharmacologic blind, the HAL DIRS-C score was found to be significantly related to study retention, ongoing psychosocial treatment participation, urinalysis results, and other measures of outcome. The results support the validity of the HAL DIRS-C as a standardized measure of improvement or outcome in clinical research involving the treatment of cocaine abuse.     

Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients

The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy.     

Meta-analysis of depression and substance use and impairment among cocaine users

BACKGROUND: The study evaluated, among cocaine users, the hypothesized positive association of depression and concurrent cocaine use and impairment, alcohol use and impairment, and general drug use and impairment. The hypothesis that gender would moderate these associations, with women showing a stronger correlation between depression and measures of substance use and impairment, was also tested. Also examined was the association of depression with future cocaine use and impairment and substance use treatment participation. METHODS: Empirical reports on adult cocaine users published in English in peer-reviewed journals since 1986 that contained data on depression and substance use outcome(s) were obtained using a systematic search. Studies that placed restrictions on range of depression scores to select the sample, experiments that administered cocaine to subjects, and trials of antidepressant medications were excluded. The search yielded 60 studies for the analysis including 53 reports that collected data from clinical venues and seven that were community-based. RESULTS: As hypothesized, the analyses showed that depression is associated with concurrent cocaine-, alcohol-, and general drug use and impairment. Effect sizes were small. Hypothesized moderating effects of gender were not supported. Depression was not associated, at a statistically significant level, with treatment participation or future cocaine use and impairment. CONCLUSIONS: Depression is consistently but modestly associated with measures of cocaine-, alcohol-, and general drug use and impairment among cocaine users. Associations of depression with treatment participation and with future cocaine use and impairment are not immediately evident, although limitations of data warrant cautious interpretation.     

Depression as a prognostic factor for pharmacological treatment of cocaine dependence.

Pharmacotherapy response in depressed (n = 20) vs. nondepressed (n = 74) cocaine-abusing methadone maintenance patients was compared in a 12-week, randomized, double-blind trial using amantadine at 300 mg daily (n = 33), desipramine at 150 mg daily (n = 30), and placebo (n = 31). Starting in Week 3, the depressed patients on medications reported significantly less cocaine usage than the depressed patients who received placebo. By Week 10, the medicated depressed patients (in treatment) reported a 96 percent decrease in cocaine usage and a 68 percent decrease in cocaine craving. During the last 2 weeks of treatment, 42 percent of the urine toxicologies of the medicated depressed patients were cocaine free, compared with only 6 percent of the placebo depressed patients. Also, the placebo nondepressed patients had significantly better treatment outcome compared with the placebo depressed patients. Thus, depression appears to be an important predictor of poor treatment outcome with relapse prevention therapy alone and of good response to cocaine abuse treatment with medication.     

Increased Depression and Anxiety Symptoms are Associated with More Breakdowns in Cognitive Control to Cocaine Cues in Veterans with Cocaine Use Disorder

Objective: Cue-elicited craving is a clinically important aspect of cocaine addiction directly linked to cognitive control breakdowns and relapse to cocaine-taking behavior. However, whether craving drives breakdowns in cognitive control toward cocaine cues in veterans, who experience significantly more co-occurring mood disorders, is unknown. The present study tests whether veterans have breakdowns in cognitive control because of cue-elicited craving or current anxiety or depression symptoms. Methods: Twenty-four veterans with cocaine use disorder were cue-exposed, then tested on an antisaccade task in which participants were asked to control their eye movements toward cocaine or neutral cues by looking away from the cue. The relationship among cognitive control breakdowns (as measured by eye errors), cue-induced craving (changes in self-reported craving following cocaine cue exposure), and mood measures (depression and anxiety) was investigated. Results: Veterans made significantly more errors toward cocaine cues than neutral cues. Depression and anxiety scores, but not cue-elicited craving, were significantly associated with increased subsequent errors toward cocaine cues for veterans. Conclusions: Increased depression and anxiety are specifically related to more cognitive control breakdowns toward cocaine cues in veterans. Depression and anxiety must be considered further in the etiology and treatment of cocaine use disorder in veterans. Furthermore, treating depression and anxiety as well, rather than solely alleviating craving levels, may prove a more effective combined treatment option in veterans with cocaine use disorder.     

The impact of sertraline,desipramine, and placebo on psychomotor functioning in depression

Impairment of psychomotor performance is a common adverse effect of many antidepressants, particularly tricyclics. Desipramine is thought to be an exception, with possible performance enhancing effects on psychomotor function. This multicentre study examined the relative effects on psychomotor function of sertraline versus desipramine versus placebo in mild to moderate depression. Fifty-eight patients who satisfied DSM-III-R criteria for major depression and had a minimum HAM-D score of 15 (17 items) completed eight weeks of treatment. They underwent a standardized assessment which included depression and anxiety rating scales (HAM-D, HAM-A, MADRS) and a battery of psychomotor performance tests (The Simple and Choice Reaction Time, The Digit Symbol Substitution and The Trail Making Test), before, during, and after eight weeks of treatment with sertraline, desipramine, or placebo. At baseline, there was a trend for both the sertraline and placebo groups to exhibit better psychomotor performance than desipramine. No significant differences were found between groups after treatment nor between groups for the change from baseline to week 8. However, at week 3, the sertraline group performed significantly better in the trail making test than the placebo patients (p<0.05). Within each treatment group, there was a trend towards improvement in performance for all four parameters from baseline to the end of the study, with these improvements being most obvious in the desipramine group. Sertraline, however, was found to be associated with significantly fewer other adverse effects than the desipramine group, i.e. sweating, dry mouth, anorexia. These results suggest that desipramine and sertraline do not adversely affect psychomotor performance and may even enhance it in mild to moderately depressed patients.     

Mood changes during prednisone bursts in outpatients with asthma.

Corticosteroids, such as prednisone and dexamethasone, are frequently prescribed medications sometimes associated with severe systemic side effects. Currently there are limited data regarding the psychiatric side effects of these medications, although mood changes and even psychoses have been reported. This study was designed to quantify psychiatric changes during brief courses of prednisone in patients with asthma. Outpatients with asthma (N = 32) receiving bursts of prednisone (>40 mg/day) were evaluated before, during, and after corticosteroid therapy by use of the Hamilton Rating Scale for Depression, the Young Mania Scale, the Brief Psychiatric Rating Scale, and the Internal State Scale. A Structured Clinical Interview for DSM-IV disorders was also conducted to examine past psychiatric history. Highly significant increases in the Young Mania Scale and Activation subscale of the Internal State Scale (both measures of mania) were observed with no increase in depression measures during the first 3 to 7 days of prednisone therapy. Mood changes were not correlated with improvement in airway obstruction, suggesting that mood elevations may not be in response to improvement in asthma symptoms. Subjects with past or current symptoms of depression had a significant decrease in depressive symptoms during prednisone therapy compared with those without depression. Some patients with posttraumatic stress disorder reported increases in depression and memories of the traumatic event during prednisone therapy. In summary, statistically significant changes in mood were observed even during brief courses of corticosteroids at modest dosages. The symptoms were primarily manic, not depressive. Persons with depression did not become more depressed during prednisone therapy, and, in fact, some showed improvement.     

Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity

Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.     

A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (-14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (-20.9) than the PLA group (-10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.     

A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence

INTRODUCTION: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric disorder. Cocaine use is particularly common in patients with bipolar disorder. Both cocaine use and bipolar disorder are associated with mood symptoms and cognitive impairment. Therefore, treatments that stabilize mood, improve cognition, and reduce cocaine use would be useful. Citicoline modulates phospholipids metabolism and neurotransmitter levels and appears to improve cognition in some central nervous system disorders. A 12-week, randomized, placebo-controlled, parallel-group, add-on, proof-of-concept trial of citicoline was conducted in 44 outpatients with a history of mania or hypomania and cocaine dependence. The primary aim was to examine memory, but mood and cocaine use were also assessed. METHOD: Participants were evaluated with a structured diagnostic interview; Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, and Rey Auditory Verbal Learning Test. Cocaine use was assessed with urine drug screens. Data were analyzed using mixed-model analysis of covariance, generalized estimating equations, and logistic regression analyses that used all of the available data. RESULTS: A significant group effect (P = 0.006) favoring citicoline was observed on the Rey Auditory Verbal Learning Test alternative word list. No significant between-group differences were found on the Inventory of Depressive Symptomatology-Self-Report or Young Mania Rating Scale. The citicoline group had a significantly lower probability of a cocaine-positive urine at exit (P = 0.026). The covariate-adjusted odds ratio estimate was 6.41, suggesting that those who took placebo had 6.41-times higher odds of testing positive for cocaine at exit than those who took citicoline. Citicoline was well tolerated, with no participants to our knowledge discontinuing because of medication side effects. CONCLUSIONS: The use of citicoline was associated with improvement relative to placebo in some aspects of declarative memory and cocaine use, but not mood. The findings are promising and suggest that larger trials of citicoline are warranted.     

Antipsychotic drugs in cocaine dependence: A systematic review and meta-analysis

A systematic review and meta-analysis to evaluate the efficacy of antipsychotic drugs in subjects with cocaine dependence is presented. Twelve randomized, double-blind, placebo-controlled clinical trials involving 681 patients were included. Five outcome measures were evaluated: number of dropouts, cocaine use assessed by means of urine benzoylecgonine tests, self-reported cocaine use, craving and Addiction Severity Index. On average, 48% of the enrolled participants were lost to follow-up. In comparison to placebo, antipsychotics did not significantly reduce cocaine use (WMD = 0.01, 95%CI = − 0.12 to 0.13) or improve retention in treatment (RR 0.91, 95%CI = 0.82–1.02). Risperidone reduced slightly dropouts in comparison to placebo (RR = 0.87; 95%CI = 0.79–0.97). To date there is insufficient evidence to justify the use of antipsychotic drugs for cocaine dependence.     

A randomized, double-blind, placebo-controlled study of ritanserin pharmacotherapy for cocaine dependence

Eighty cocaine-dependent individuals enrolled in outpatient treatment took part in a randomized, double-blind, placebo-controlled trial of ritanserin, a 5-HT(2) antagonist, as an adjunct therapy. Participants attended an outpatient day hospital therapy program each day and received tablets containing placebo or 10 mg ritanserin for a 4-week period. Primary outcome measures included retention in treatment, urine drug tests, and self-reports of craving. Secondary outcome measures were depression scores on the Beck and Hamilton inventories, negative mood as measured by the Profile of Mood States, and life functioning as measured by the Addiction Severity Index. Although participants showed improvement over the 4 weeks, there were no group differences on any of the measures. These results fail to support the use of ritanserin as a complement to outpatient psychosocial therapy for cocaine dependence.     

Impact of Desipramine or Carbamazepine on Patient Retention in Outpatient Cocaine Treatment:

This is a preliminary report of a double-blind comparison of desipramine or carbamazepine to placebo among subjects participating in an outpatint cocaine treatment program. Sixty-five subjects were randomly assigned to one of the active drugs or placebo and followed until treatment completion or drop-out to determine if either drug enhanced retention in treatment and/or increased cocaine abstinence. There was no significant difference between carbamazepine or desipramine and placebo on either outcome measure in this preliminary analysis. While this is a preliminary report and does not take into account the heterogenity of the patients in cocaine treatment, the results are consistent with those of other investigators and suggest that the use of desipramine or carbamazepine may not offer any advantage in retaining cocaine-dependent patients in treatment.     

Buspirone in depressed outpatients: a controlled study

One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day.     

Psychosocial functioning and cocaine use during treatment: strength of relationship depends on type of urine-testing method

Although improvement in psychosocial functioning is a common goal in substance-abuse treatment, the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use. However, the relationship between cocaine use and psychosocial outcomes is not well documented. To investigate this relationship and identify the optimal urine-screen method, we retrospectively analyzed data from two 25-week randomized controlled trials of abstinence reinforcement (AR) in 368 cocaine/heroin users maintained on methadone. Cocaine use was measured thrice weekly by qualitative urinalysis, benzoylecgonine concentration (BE), and an estimate of New Uses of cocaine by application of an algorithm to BE. Social adjustment (SAS-SR), current diagnosis of cocaine dependence (DSM-IV criteria), and depression symptoms (Beck Depression Inventory) were determined at study exit. Cocaine use was significantly lower in AR groups than in controls. Across groups, in-treatment cocaine use was significantly associated with worse social adjustment, current cocaine dependence, and depression at exit. Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE. Nevertheless, the amount of variance accounted for by the urine screens was typically <15%. Cocaine use during treatment, especially when measured with New Uses criteria, can predict psychosocial functioning, but cannot substitute for direct measures of psychosocial functioning.