Johannes Strasser

Treatment or “high”: Benzodiazepine use in patients on injectable heroin or oral opioids

Benzodiazepine (BZD) use is widespread among opioid-maintained patients worldwide. We conducted a cross-sectional survey to investigate motives and patterns of BZD use and psychiatric comorbidity in a convenience sample of patients (n=193) maintained on oral opioid agonists or diacetylmorphine (DAM). Prolonged BZD use and high-risk behaviors like parenteral use were common. After principal component analysis, motives were divided into those related to negative affect regulation, positive affect regulation (i.e. reward-seeking) and somato-medical problems. Negative affect regulation and somato-medical motives were associated with prolonged use. Psychiatric comorbidity was associated with several self-therapeutic motives, most importantly to lose anxiety. Patients maintained on DAM were more likely to be ex-users of BZD and report high positive affect regulation. Therefore, patients maintained on different agonists may have deviating motives for BZD use, which could be of importance when addressing this issue. Treatment of psychiatric comorbidity, in particular anxiety, depressive and sleeping disorders, may be helpful in reducing BZD use, particularly in patients maintained on oral opioids.

A randomized, controlled, pilot trial of methylphenidate and cognitive-behavioral group therapy for cocaine dependence in heroin prescription.

Abstract Cocaine dependence has proved difficult to treat, whether it occurs alone or in combination with opiate dependence. No intervention has been demonstrated to be uniquely effective. Patients might benefit most from combined pharmacotherapeutic and psychotherapeutic interventions. The present study sought to evaluate the feasibility, tolerability, and efficacy of methylphenidate (MP) and cognitive-behavioral group therapy (CBGT) for cocaine dependence in diacetylmorphine-maintained patients. Sixty-two cocaine-dependent diacetylmorphine-maintained patients participated in a dual-site, double-blind, placebo-controlled pilot trial with 4 treatment conditions. The participants were randomly assigned to receive MP or a placebo each combined with either CBGT or treatment as usual for 12 weeks. Methylphenidate 30 mg and a placebo in identical capsules were administered onsite twice daily under supervision in a fixed-dose regimen without titration. Manual-guided CBGT consisted of 12 weekly sessions. Participation in the CBGT sessions was voluntary. Primary outcome measures were retention in pharmacologic treatment, cocaine-free urine samples, self-reported cocaine use, and adverse effects. Urine screens were performed thrice weekly. Seventy-one percent of the participants completed the study protocol. Methylphenidate was well tolerated with similar retention rates compared with the placebo. No serious adverse effects occurred. No difference in cocaine-free urine screens was found across the 4 treatment groups. Self-reported cocaine use was reduced in all 4 study groups. Methylphenidate and CBGT did not provide an advantage over a placebo or treatment as usual in reducing cocaine use. There were no signs of additive benefits of MP and CBGT. Because of the small sample size, the results are preliminary.

Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by specific study characteristics, among them dosing, duration of treatment, or sample size. This needs to be considered when discussing the potential of MPH as replacement therapy for cocaine dependence. Finally, based on the results, we suggest possible directions for future research.

A randomized, controlled trial of combined cognitive-behavioral therapy plus prize-based contingency management for cocaine dependence

BACKGROUND Cocaine has become one of the drugs of most concern in Switzerland, being associated with a wide range of medical, psychiatric and social problems. Available treatment options for cocaine dependence are rare. The study sought to compare combined prize-based contingency management (prizeCM) plus cognitive-behavioral therapy (CBT) to CBT alone in cocaine-dependent patients. METHODS Sixty cocaine-dependent patients participated in a randomized, controlled trial with two treatment conditions. The participants were randomly assigned to the experimental group (EG; n = 29), who received CBT combined with prizeCM, or to the control group (CG; n = 31), who received CBT only during 24 weeks. The primary outcome measures were retention, at least 3 consecutive weeks of cocaine abstinence, the maximum number of consecutive weeks of abstinence and proportions of cocaine-free urine samples during the entire 24-week and at 6-month follow-up. RESULTS Sixty-three percent of the participants completed the study protocol. Participants in both groups significantly reduced cocaine use over time. Overall, no difference in cocaine-free urine screens was found across the two treatment groups, except at weeks 8, 9, 10, 17 and 21 in favor of the EG. CONCLUSIONS The addition of prizeCM to CBT seems to enhance treatment effects, especially in the early treatment period, supporting results from previous studies. Both the combined intervention and CBT alone, led to significant reductions in cocaine use during treatment and these effects were sustained at 6-month follow-up. These findings underline the importance in implementing CM and CBT interventions as treatment options for cocaine dependence in the European context.

Optimizing heroin-assisted treatment (HAT): Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use

BACKGROUND Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites. METHOD Fifty-four patients in HAT were recruited from the centre for HAT at the University of Basel, Switzerland. The patients completed the Alcohol Use Disorder Identification Test (AUDIT), a self-report questionnaire on past-week ethanol intake and provided samples for the determination of ethyl glucuronide (UEtG) and ethyl sulphate (UEtS) in urine and of ethyl glucuronide (HEtG) in hair. RESULTS Eighteen patients scored above the AUDIT cut-off levels. Twenty-six patients tested positive for UEtG and 29 for UEtS. HEtG identified ethanol intake of more than 20 g/d in 20 additional cases that did not appear in the AUDIT. Using the total score of the AUDIT, HEtG detected 14 additional cases of relevant alcohol intake. CONCLUSIONS The findings of this study, which is the first assessing alcohol intake in HAT patients using direct ethanol metabolites and self reports, suggest the complementary use of both. Improved detection of hazardous or harmful alcohol consumption in the context of HCV and heroin dependence will allow for earlier intervention in this population. This ultimately will contribute to an improvement in quality of life of patients in HAT. Furthermore, a significant reduction of costs can be achieved through a reduction of complications caused by alcohol intake.

Similar and Different? Subjective Effects of Methylphenidate and Cocaine in Opioid-Maintained Patients

ABSTRACT Methylphenidate (MPH) is commonly prescribed for attention deficit hyperactivity disorder (ADHD). Recreational nonmedical use has been described and also occurs in patients on opioid maintenance treatment (OMT). MPH has been proposed for use as replacement therapy in cocaine dependence, although evidence for efficacy is inconclusive. We conducted a cross-sectional interview study on patterns of MPH use in a sample of 20 MPH-using patients on OMT with a history of cocaine use. We assessed symptoms of depression, ADHD during childhood, and retrospective subjective-effects profiles of MPH and cocaine. Risky patterns of MPH use were common, in particular illicit acquisition, use of high doses, and parenteral administration. Sixty percent of patients reported having used MPH as a substitute for cocaine. Correspondingly, the subjective-effect profiles of MPH and cocaine showed striking parallels, with overall effects of MPH being rated more positively than those of cocaine. Proportions of patients with elevated scores for depression or childhood ADHD were large, highlighting the importance of treating dual disorders in this population. Clinical studies on MPH substitution in cocaine-dependent patients on opioid maintenance treatment could benefit from consideration of the patterns of application of MPH in this population. Results are preliminary due to small sample size.

Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the “Bernese method”

Background Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use. Cases We present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms. Discussion Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction.

Psychosis After Switch in Opioid Maintenance Agonist and Risperidone-Induced Pisa Syndrome: Two Critical Incidents in Dual Diagnosis Treatment

ABSTRACT Background and aims: Dual diagnosis commonly occurs among patients with an opioid use disorder. Treatment is ideally performed in an integrated fashion. We present a case that illustrates the complex and challenging psychiatric and medical therapy of such patients in the light of the literature. Case description: We report on a 56-year-old patient with schizophrenia and opioid dependence who experienced both risperidone-induced Pisa syndrome and, 3 years later, acute psychosis after switching the opioid substitution medication from methadone to slow-release oral morphine due to QT prolongation. Conclusions: With the current availability of a diversity of substitution opioids in Switzerland (methadone, buprenorphine, diacetylmorphine, sustained-release oral morphine), studies on differential effectiveness of these agents in opioid-dependent subpopulations with selective comorbidity profiles are desirable. The same is true for further investigation of the involvement of the opioid receptor system in schizophrenia. In clinical practice, any alteration of opioid medication in patients with dual diagnosis and a history of schizophrenia should be accompanied by close observation for psychotic symptoms.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting

Background: Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. Methods: All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Results: Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient’s therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Conclusions: Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient’s empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Novel Medication Supply Model Guarantees Adequate Management and High Adherence to Polypharmacy in Older Opioid Users – Preliminary Results with Outpatients

Background: Life expectancy of older drug users has increased, primarily thanks to opioid agonist treatment (OAT). Nursing homes are often not adapted to accommodate patients with substance use disorders. Although care and adherence to polypharmacy in older opioid users need considerable resources e.g., daily visits to an outpatient clinic, outpatient treatment and surveillance are provided as long as possible. We developed a novel medication supply model with an electronic dispenser of pre-packed medications located at patient home, after allowing for law requirements concerning the dispensing of opioids, and present preliminary results from three illustrative outpatients. Methods: The community pharmacy provided unit-of-dose pouches with all solid oral medications directly to patient home. Opioids for substitution were obtained at the addiction clinic in at least weekly intervals, otherwise in the pouches. The pouches were loaded into a lockable, remote-controlled medication management aid that was programmed according to the patient’s medication schedule. The dispenser reminds patients with acoustic alerts to take their medication and records dates and times of medication retrievals. It automatically sends an alert if a patient misses to retrieve a dose. Results: Our three outpatients used the electronic dispenser during 659, 118 and 61 days, with a total of 5, 9, and 18 pills to take daily at 1, 3 and 5 intake times, respectively. The majority of the doses were taken on the preset time (94%, 68.2% and 73.7%) or deliberately in advance (pocket dose). Clinical benefits were initiation and maintenance of a therapy for dementia over 18 months and suppression of HIV viral load over 1.8 years (patient 1), prevention of further dose escalation of pain medication (patient 2) and release of prompts to initiate the existential task of cooking (patient 3). Conclusion: Our novel supply model allows adequate implementation and persistence of complex treatments with outpatients. Clinical outcomes improved, patients and caregivers were satisfied, and resources were saved.