Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.

BACKGROUND: A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence. METHODS: This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date. RESULTS: Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men. CONCLUSIONS: Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.

Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence: efficacy of contingency management and significant other involvement.

BACKGROUND: Contingency management (CM) and significant other involvement (SO) were evaluated as strategies to enhance treatment retention, medication compliance, and outcome for naltrexone treatment of opioid dependence. METHODS: One hundred twenty-seven recently detoxified opioid-dependent individuals were randomly assigned to 1 of 3 conditions delivered for 12 weeks: (1) standard naltrexone treatment, given 3 times a week; (2) naltrexone treatment plus contingency management (CM), with delivery of vouchers contingent on naltrexone compliance and drug-free urine specimens; or (3) naltrexone treatment, CM, plus significant other involvement (SO), where a family member was invited to participate in up to 6 family counseling sessions. Principal outcomes were retention in treatment, compliance with naltrexone therapy, and number of drug-free urine specimens. RESULTS: First, CM was associated with significant improvements in treatment retention (7.4 vs 5.6 weeks; P =.05) and in reduction in opioid use (19 vs 14 opioid-free urine specimens; P =.04) compared with standard naltrexone treatment. Second, assignment to SO did not significantly improve retention, compliance, or substance abuse outcomes compared with CM. Significant effects for the SO condition over CM on retention, compliance, and drug use outcomes were seen only for the subgroup who attended at least 1 family counseling session. The SO condition was associated with significant (P =.02) improvements in family functioning. CONCLUSION: Behavioral therapies, such as CM, can be targeted to address weaknesses of specific pharmacotherapies, such as noncompliance, and thus can play a substantial role in broadening the utility of available pharmacotherapies.

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic.

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use. SUBJECTS AND METHODS: Opioid-dependent patients were randomly assigned to receive thrice weekly buprenorphine maintenance in a primary care clinic that was affiliated with a drug treatment program (n = 23) or in a traditional drug treatment program (n = 23) in a 12-week clinical trial. Primary outcomes were retention in treatment and urine toxicology for opioids; secondary outcomes were opioid withdrawal symptoms and toxicology for cocaine. RESULTS: Retention during the 12-week study was higher in the primary care setting (78%, 18 of 23) than in the drug treatment setting (52%, 12 of 23; P = 0.06). Patients admitted to primary care had lower rates of opioid use based on overall urine toxicology (63% versus 85%, P < 0.01) and were more likely to achieve 3 or more consecutive weeks of abstinence (43% versus 13%, P = 0.02). Cocaine use was similar in both settings. CONCLUSIONS: Buprenorphine maintenance is an effective treatment for heroin dependence in a primary care setting.

Rates of personality disorders in substance abusers: a comparison between DSM-III-R and DSM-IV.

The publication of the DSM-IV represents the first revision in 7 years to the DSM-III-R diagnostic criteria. The purpose of the current study is to evaluate the impact of changes to the Axis II criteria on diagnostic rates in a substance abusing population. We interviewed 370 patients entering treatment using a modified version of the SCID-II, which allowed for the diagnosis of both DSM-III-R and DSM-IV Axis II diagnoses. Prevalence rates for each Axis II disorder are given, as well as kappa statistics showing diagnostic agreement between the two systems. The results of this study indicate good rates of diagnostic agreement between the two systems with a few notable exceptions. Poor rates of diagnostic agreement were obtained for the histrionic and dependent diagnostic categories. No single diagnostic change appears to be responsible for the prevalence rate differences between the two systems.

Substance dependence posttraumatic stress disorder therapy. An integrated cognitive-behavioral approach.

While substance abuse and posttraumatic stress disorder (PTSD) are known to frequently co-occur, there have been few published clinical trials evaluating integrated approaches for this form of dual diagnosis. This article describes Substance Dependence PTSD Therapy (SDPT), the first manualized individual treatment to undergo a controlled clinical trial. SDPT is a 5-month, twice-weekly, two-phase individual cognitive-behavioral treatment utilizing (a) relapse prevention and coping skills training for substance abuse; and (b) psychoeducation, stress inoculation training, and in vivo exposure for PTSD. SDPT is also unique in having been designed for use in mixed-gendered civilians with varied sources of trauma. Design considerations and the format, structure, and content of therapy sessions are discussed. Open trial pilot data indicates efficacy in reducing PTSD severity.

An open trial of EMDR as treatment for chronic PTSD.

In a prepilot study, eight adults with chronic PTSD underwent three 90-minute sessions of eye movement desensitization and reprocessing (EMDR) at one-week intervals in an open trial. None of the seven who completed treatment met criteria for current PTSD two months later. Significant decreases in measures of pathology and disturbance were recorded. A controlled trial of EMDR is under way.

Childhood trauma and posttraumatic stress disorder in substance abuse inpatients.

This pilot study examined: the prevalence of childhood trauma in a sample of male veteran substance abuse inpatients, and the relationship of childhood trauma to substance abuse in this sample, controlling for posttraumatic stress disorder (PTSD). Forty-six subjects were interviewed using the Traumatic Antecedents Questionnaire, Structured Clinical Interview for DSM-III-R (SCID)-P Psychoactive Substance Use Disorders module, the Addiction Severity Index, and the SCID-NP-V PTSD module. Seventy-seven percent of subjects had been exposed to severe childhood trauma. Fifty-eight percent had lifetime PTSD. The total number of lifetime substance dependence disorders was strongly positively associated with total childhood trauma exposure. This relationship remained significant after controlling for demographics, family history of alcohol problems, combat exposure, and lifetime PTSD, including combat-related PTSD. A substantial number of these subjects reported exposure to childhood trauma, which in turn was related to multiple substance dependence. This has important implications for the natural history and prevention of multiple substance dependence disorders.

Personality disorders in substance abusers: relation to substance use.

Previous studies have documented high but variable rates of DSM personality disorders (axis II) in clinical samples of substance abusers. Distinguishing between personality disorder symptoms that are independent versus substance-related (SR) is a particular challenge for diagnosing comorbid axis II disorders in substance abusers. DSM-IV guidelines currently recommend excluding axis II symptoms that are accounted for by an axis I disorder, including a substance use disorder. In this study, axis II diagnoses were made on a heterogenous clinical sample of 370 patients entering treatment for substance use disorders. Axis II diagnoses were made according to DSM-III-R criteria using the Structured Clinical Interview for DSM-III-R (SCID-II), which was modified to determine, on an item-by-item basis, whether symptoms were attributed to subjects' substance use disorders or independent of these disorders. The majority (57.0%) of substance use disorder patients met criteria for at least one comorbid axis II disorder, with cluster B (45.7%) being particularly prominent, especially antisocial personality disorder (ASP) (27.0%) and borderline personality disorder (BPD) (18.4%). Notably, inclusion of SR symptoms led to a substantial number of newly diagnosed cases, especially for ASP (19.2%) and BPD (11.4%). Including SR symptoms improved the reliability of ASP and did not change the reliability of BPD diagnoses. Generally, patients with SR and independent personality disorders had a similar clinical profile.

Continuity of care and desipramine in primary cocaine abusers.

The objective of this research was to determine the efficacy of enhanced continuity of care and desipramine in increasing treatment attendance and abstinence from cocaine in primary cocaine abusers. Study design was a random assignment, placebo-controlled factorial with assessments at baseline and at 3 (first week of outpatient treatment), 8, and 12 weeks after start of study. Desipramine blood levels were taken at weeks 2 (inpatient), 3, and 8. Subjects (N = 94 men) were recruited on an inpatient ward and assigned to increased continuity of care or to standard treatment, and to active or placebo drug. Main outcome variables were toxicology-verified reports of cocaine use, and attendance at counseling sessions. Enhanced continuity of care increased abstinence from cocaine at week 3 and increased attendance at individual counseling sessions throughout the 12 weeks of the study. There were no main effects for desipramine. Blood levels above 123 ng/ml at week 2 predicted longer stays in outpatient. We conclude that enhanced continuity of care is a low cost intervention that improves early treatment outcome and attendance; desipramine effects do not warrant its therapeutic use.

Survey of the cross-cultural content of U.S. psychiatry residency training programs.

To establish the extent of cross-cultural content contained in the 224 psychiatric residency training programs, the Directors of Residency Training were surveyed by mail. Thirty-seven percent (N = 83) of Directors responded; 92% (N = 76) had cross-cultural content, 99% (N = 82) had opportunities to work with minority patients, and 77% (N = 64) had supervision by some minority faculty. Responding programs reported a need for teaching videotapes (85%, N = 71), cross-cultural references (78%, N = 65), academic psychiatrists familiar with different cultural groups (76%, N = 63), and cross-cultural supervision (75%, N = 62).

Biosynthesis of salivary proteins in the parotid gland of the subhuman primate, Macaca fascicularis. Cell-free translation of the mRNA for a proline-rich glycoprotein and partial amino acid sequence and processing of its signal peptide.

The major anionic proline-rich proteins in the parotid and submandibular secretions of subhuman primates and man perform the important biological function of inhibiting crystal growth of calcium phosphate salts from saliva, which is supersaturated with calcium phosphate salts, thereby preventing excess deposition of hydroxylapatite on tooth surfaces. The present work was initiated as a first step towards investigating proline-rich protein biosynthesis in parotid glands using the subhuman primate, Macaca fascicularis, as a model system. RNA was isolated from macaque parotid glands and separated into poly(A)-enriched and poly(A)-deficient fractions by chromatography on oligo(dT)-cellulose. The mRNAs in both fractions promoted incorporation of radiolabeled amino acids into polypeptides in an mRNA-dependent reticulocyte lysate translation system. Five major proline-rich polypeptides were detected and one of these was shown to be the in vitro precursor of the major anionic macaque proline-rich protein (MPRP), which is the structural and functional counterpart of the major anionic proline-rich proteins in the parotid and submandibular secretions of man (Oppenheim, F.G., Offner, G.D., and Troxler, R.F. (1982) J. Biol. Chem. 257, 9271-9282). Radiosequencing of the material in anti-MPRP immune precipitates showed that the in vitro precursor of MPRP contained an 18-residue signal peptide. The in vitro precursor of MPRP was processed in dog pancreas vesicles to a form with a lower apparent Mr and with an NH2-terminal amino acid sequence identical to that of native MPRP. The phenylthiohydantoin derivatives of Ala and Ile were detected at residue 9 and those of Val and Met were detected at residue 16 of the signal peptide. This indicated that the in vitro precursor of MPRP, which migrated electrophoretically as a single band in anti-MPRP immune precipitates, contained two different in vitro polypeptides derived from two different mRNAs. These results are discussed in the context of the genetic polymorphism among the major anionic proline-rich proteins in the parotid and submandibular secretions of man.

A nationwide study of breast disease.

Records of histopathology from the 3734 Jewish women having breast biopsy and/or operations in all Israeli hospitals during the year from July 1979 to June 1980 were reviewed. Approximately 28.5% of these women were diagnosed as having breast cancer and 71.5% as having benign breast disease: 48.5% had benign proliferative mastopathy (BPM), 16.6% had fibroadenoma (FA) without coexistent BPM, and 6.4% had other benign breast conditions. The age-specific incidence rate was 66 in 100,000 for breast cancer and 165.2 in 100,000 for benign breast disease. Native European or American women and native Israeli women had significantly higher age standardized incidence rates of both breast cancer and BPM, but not of FA, as compared to African/Asian-born women (P less than 0.01). Age-related ratios between invasive to precursor breast lesions were similar in all ethnic groups. The data suggest that breast cancer and benign proliferative mastopathy may have a common etiologic component.

A pilot study of primary-care-based buprenorphine maintenance for heroin dependence.

The treatment of heroin dependence with opioid maintenance has traditionally employed methadone and more recently buprenorphine administered in traditional drug treatment settings. In this pilot study we evaluated buprenorphine maintenance for the treatment of heroin dependence in a program administered by primary-care providers in a primary-care setting. Seven patients were admitted to this nonblinded open-label pilot study and were offered 6 months of primary-care-based buprenorphine maintenance. Buprenorphine was administered in doses of 16 mg on Monday and Wednesday and 32 mg on Friday. Patients were seen weekly by primary-care providers and attended self-help meetings. Of the seven patients admitted to the study, five (71%) completed the 6-month pilot study and two (29%) were removed from the study. Urine toxicology data showed that the majority of urines tested were clear of opioids in four out of five patients who remained in treatment. These results suggest that primary-care-based opioid maintenance using buprenorphine shows promise as a new approach to the treatment of heroin dependence.