Patient Perspectives on Pharmacotherapy of Alcohol Dependence.

INTRODUCTION: Pharmacotherapy with drugs like naltrexone or acamprosate is a well-evaluated element in the treatment of alcohol dependence (AD). However, in many countries, these medications are rarely administered. The objective of the present study was to identify from patients' perspective factors that prevent the initiation and compliance with pharmacological treatment of AD. METHODS: Patients from inpatient alcohol withdrawal treatment underwent a standardized interview. Questions included socio-demographic data, history of AD, treatment history, knowledge and personal experience regarding pharmacotherapy of AD, and personal views about the causes of AD. RESULTS: Three hundred patients (mean age 47.3 years, 27.7% female, mean duration of AD 8.9 years, 67% with a history of previous inpatient withdrawal treatment) were included. The majority of patients (58.7%) already knew drugs for the pharmacotherapy of AD. Thirty percent had ever used such medications, most often acamprosate. Except for disulfiram, pharmacotherapy of AD had lasted only a few weeks, on average. Medication usually had been applied without additional psychotherapy. No severe side effects were reported. Patients had often stopped pharmacotherapy on their own, when assuming they had reached stable abstinence. Openness to start pharmacotherapy for AD was currently stated by 67% of the total sample. In multiple logistic regression, openness was predicted by having a concept of AD as a medical disease and by a shorter duration of AD. DISCUSSION: To improve the administration of pharmacotherapy for AD implementation strategies should be systematically developed and evaluated with a focus on the concept of AD as a medical disease.

Effectiveness of Medical Cannabis for the Treatment of Depression: A Naturalistic Outpatient Study.

BACKGROUND: There is a lack of studies on the course and effectiveness of medical cannabis in the treatment of major depressive disorder (MDD). METHODS: Retrospective longitudinal (18 weeks) study of n=59 outpatients with MDD, treated with medical cannabis via a telemedical platform. Previous treatment with antidepressant medication was required for inclusion into the study. Standardized data collection was carried out at entry and during monthly consultations. Severity of depression was measured on a 0-10 point rating scale. Side-effects were assessed by a checklist. RESULTS: Patients were 20-54 years old; 72.9% were male; one third reported times of regular cannabis consumption within the previous five years. Drop-out rate was 22% after 18 weeks. Mean severity of depression decreased from 6.9 points (SD 1.5) at entry to 3.8 points (2.7) at week 18 (baseline observation carried forward; 95% CI for the mean difference: 2.4 to 3.8; p<0.001). A treatment response (>50% reduction of the initial score) was seen in 50.8% at week 18. One third of patients complained about side effects, none was considered as severe. Concomitant antidepressant medication (31% of patients) was not associated with outcome. CONCLUSIONS: Medical cannabis was well tolerated and dropout rate was comparable to those in clinical trials of antidepressant medication. Patients reported a clinically significant reduction of depression severity. Further research on the effectiveness of medical cannabis for MDD seems warranted. Risks of this medication, such as sustaining or inducing a cannabis use disorder, or side effects such as poor concentration, must be taken into consideration.

Ten years of maintenance treatment of severe melancholic depression in an adult woman including discontinuation experiences.

BACKGROUND: There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer than 2 years and some recent studies suggested an advantage of cognitive behavioral therapy (CBT) over antidepressants in relapse prevention of MDD. METHODS: Exclusively outpatient "real world" treatment of severe melancholia, prospectively documented over 10 years with different serial treatment strategies, discontinuation phenomena and complications. METHODS: Compared to CBT, agomelatine, mirtazapine, bupropion and high-dose milnacipran, high-dose venlafaxine (extended-release form, XR) was effective, even sustainably. Asymptomatic premature ventricular contractions (PVCs) were found at the beginning of the treatment of the MDD, which initially led to the discontinuation of high-dose venlafaxine (300 mg daily). Even the various treatment strategies mentioned above were unable to compensate for or prevent the subsequent severe deterioration in MDD (2 rebounds, 1 recurrence). Only the renewed use of high-dose venlafaxine was successful. PVC no longer occurred and the treatment was also well tolerated over the years, with venlafaxine serum levels at times exceeding 5 times the recommended upper therapeutic reference level (known bupropion-venlafaxine interaction, otherwise 2.5 to 3-fold increase with high-dose venlafaxine alone). During dose reduction or after gradual discontinuation of high-dose venlafaxine, rather mild withdrawal symptoms occurred, but as described above, also two severe rebounds and one severe recurrence happened. DISCUSSION: This long-term observation supports critical reflections on the discontinuation of successful long-term treatment with antidepressants in severe MDD, even if it should be under "the protection" of CBT. The PVC seemed to be more related to the duration of the severe major depressive episode than to the venlafaxine treatment itself. A particular prospective observation of this longitudinal case study is that relapses (in the sense of rebounds) during or after previous venlafaxine tapering seemed to herald the recurrence after complete recovery. Remarkably, neither relapses nor recurrence could be prevented by CBT. CONCLUSION: In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability.

Cannabis use, abuse and dependence during the COVID-19 pandemic: a scoping review.

The interaction between cannabis use or addiction and SARS-COV-2 infection rates and COVID-19 outcomes is obscure. As of 08/01/2022 among 57 evaluated epidemiological/clinical studies found in Pubmed-database, most evidence for how cannabis use patterns were influenced by the pandemic was given by two systematic reviews and 17 prospective studies, mostly involving adolescents. In this age group, cannabis use patterns have not changed markedly. For adults, several cross-sectional studies reported mixed results with cannabis use having increased, decreased or remained unchanged. Two cross-sectional studies demonstrated that the severity of adults´ cannabis dependence was either increased as a consequence of increasing cannabis use during the pandemic or not changed. Regarding the effect of cannabis use on COVID-19 outcomes, we found only five retrospective/cross-sectional studies. Accordingly, (i) cannabis use did not impact mild COVID-19 symptoms; (ii) cannabis using individuals experienced more COVID-19-related hospitalizations; (iii) cannabis using veterans were associated with reduced SARS-COV-2 infection rates; (iv) frequent cannabis use was significantly associated with COVID-19 mortality, and (v) cannabis dependents were at higher risk of COVID-19 breakthrough after vaccination. It should be outlined that the validity of these retrospective/cross-sectional studies (all self-reports or register/e-health-records) is rather low. Future prospective studies on the effects of cannabis use on SARS-COV-2 infection rates and COVID-19 outcomes are clearly required for conclusive risk-benefit assessments of the role of cannabis on users' health during the pandemic. Moreover, substance dependence (including cannabis) is associated with (often untreated) somatic comorbidity, which severity is a proven key risk factor for worse COVID-19 outcomes.

How Effective is a Web-Based Mental Health Intervention (Deprexis) in the Treatment of Moderate and Major Depressive Disorders when started during Routine Psychiatric Inpatient Treatment as an Adjunct Therapy? A Pragmatic Parallel-Group Randomized Controlled Trial.

BACKGROUND: Internet-based self-help-programs like deprexis have been increasingly shown to reduce depressive symptoms if added to distinct, primarily outpatient-treatment-settings. There is limited information about the effectiveness of deprexis if started at routine psychiatric hospital inpatient treatment of moderate-to-severe major depressive disorder (MDD). SUBJECTS AND METHODS: To examine, sixty-nine adult MDD-inpatients were randomly assigned to a 12-week-period of treatment-as-usual (TAU, N=33) or TAU plus guided deprexis (TAU-PLUS, N=36). The study was planned as a pragmatic approach considering psychiatric routine conditions, particularly, offering an instant and flexible discharge management when the patients felt stabilized enough for primary/secondary care. Therefore, there was no fixed time frame for the inpatient treatment duration. Post-discharge, patients were followed by structured telephone interviews up to study-endpoint, i. e., 12 weeks after deprexis-initiation. Primary (Beck-Depression-Inventory-II, BDI-II) and secondary outcome-measures (Hamilton-Depression-Scale, Clinical-Global-Impression-Severity, WHO-Well-Being-Index, Helping-Alliance-Questionnaire) were carried out at study entry and every 2 weeks. Furthermore, the working alliance with deprexis as well as the inpatient treatment duration, the daily activity and the utilization of post-hospital care after discharge were determined. RESULTS: At week 12, modified ITT-analyses showed significant between-group differences of BDI-II scores in favor of the TAU-PLUS-patients (p=.03) corresponding to a medium effect size (d=-.73, 95% CI -1.4 to .06). TAU-PLUS-patients showed greater daily activity (p=.04, d=.70, 95% CI -.03 to 1.38) and had been discharged significantly earlier from inpatient treatment (p=.003). Post-discharge, the TAU-PLUS-group reported a lower rate of post-hospital care (p=.01) and re-admissions (p=.04). Secondary outcome-measures including the alliance with the therapists were not significantly different between the groups at study-endpoint. The patients´ working-alliance with deprexis significantly predicted MDD-improvement and wellbeing. Both groups (TAU and TAU plus deprexis) were comparable with regard to the prescribed antidepressant medication. Unfortunately, detailed data on the amount and actual duration of the psychotherapeutic and special therapeutic individual and group settings of the TAU were not collected CONCLUSION: TAU plus deprexis was superior to TAU in improving subjective depression-severity (BDI-II) and daily activity in patients having sought psychiatric inpatient MDD-treatment before. This beneficial effect appeared 12 weeks after inpatient deprexis-initiation, i. e. when the vast majority of patients were back in primary/secondary care. Adjunctive deprexis was associated with earlier discharges and a significant advantage for post-hospital stabilization. In this regard, it could be promising to include deprexis into inpatient treatment conditions, thereby also preparing its continuing outpatient use. We found no evidence that deprexis interfered negatively with the alliance between the patients and their therapists.

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants-A Scoping Review.

PURPOSE/BACKGROUND: Studies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2-infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19. METHODS/PROCEDURES: We conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19. FINDING/RESULTS: As of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19-related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate. IMPLICATIONS/CONCLUSIONS: At present, the best evidence of an "anti-COVID-19" potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute "dark zones" in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

How prevalent and severe is addiction on GABAmimetic drugs in an elderly German general hospital population? Focus on gabapentinoids, benzodiazepines, and z-hypnotic drugs.

OBJECTIVE: Gabapentinoids (GPT) are reported to be increasingly misused by opioid- and polydrug-users, but the addictive potential of GPT outside of these populations remains understudied. Investigations comparing GPT abuse and dependence liability to that of other commonly prescribed Central Nervous System-acting medications are therefore warranted. We provide a comparison of GPT-abuse/dependence to that of other GABAmimetics within an elderly population. DESIGN: DSM-IV-TR-based data (previously prospectively collected by SKID-I-interview) from a random sample of elderly patients admitted to a metropolitan German general hospital were reviewed. The prevalence and severity of GPT, benzodiazepine (BDZ), and z-hypnotic drug (ZD)-abuse and -dependence were compared, stratified also by mono-substance (no concurrent current or previous substance use) and de novo-substance (first)-abuse and -dependence states. RESULTS: Among 400 patients (75 ± 6.4 years old; 63% females), neither current nor past abuse of BDZ, ZD or GPT, nor other illicit substances was observed. Dependence upon BDZ, ZD or GPT was observed among 55 (13.75%) individuals. The related lifetime/12-month prevalence-rates were: dependence condition (BDZ: 7%/2.45%; ZD: 4.25%/4.25%; GPT: 2.75/2.5%); mono-dependence condition (BDZ: 2.25%/0.75%; ZD: 1%/1%, GPT: 0%/0%); de novo-dependence condition (BDZ: 2.75%/1.75%; ZD: 1%/1%, GPT: 0.5%/0.5%). Opioid analgesic-dependence (N = 43/400) was significantly more frequently linked with BDZ than with GPT (p < 0.01) [Correction added on 29 December 2021, after first online publication: In the sentence 'Opioid analgesic-dependence…', the term 'and ZD' has been deleted]. For all three GABAmimetic classes, most mono- and de novo-dependence states were mild-to-moderate and lasted 2-6 years (median). CONCLUSION: GABAmimetic-dependence was usually mixed with other substance-dependences. Every third to fourth instance of BDZ- or ZD-dependence was a mono-dependence condition, while a pure GPT-dependence was absent in this elderly (and illicit substance-naïve) population.

Impact of Psychiatric and Related Somatic Medications on the Duration and Severity of COVID-19: A Retrospective Explorative Multi-center Study from the German Metropolitan Ruhr-area.

INTRODUCTION: Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes. METHODS: In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms. RESULTS: COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56-95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study. DISCUSSION: None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.

[Evaluation of the Effectiveness of the Clarification-Oriented Psychotherapy in Persons with a Narcissistic Personality Disorder According to DSM-IV - A Naturalistic Longitudinal Study with Pre-Post Design]. / Evaluation der Wirksamkeit der klärungsorientierten Psychotherapie bei Personen mit einer narzisstischen Persönlichkeitsstörung nach DSM-IV ­ eine naturalistische Längsschnittstudie mit prä-post Design.

BACKGROUND: The treatment of patients diagnosed with a narcissistic personality disorder (NPS) is considered to be extra challenging. Well-controlled studies on the effectiveness of psychotherapy in NPS patients are not available; so many interventions are based on theoretical constructs. The clarification-oriented psychotherapy (COP) is a psychotherapeutic approach, which emerged from concepts of the cognitive behavioral therapy, client-centered psychotherapy and various process-oriented procedures. The present ambulatory therapy-evaluation of COP aimed to evaluate the effectiveness of a psychotherapeutic treatment for patients suffering from NPS. METHODS AND RESULTS: Retrospective cohort-study including 173 treatment-seeking NPS-patients. Via pre-post per-protocol-analysis, significant improvements mostly with medium effect sizes were found in all relevant parameters after completion of the COP (58.6±10.5 sessions). In particular, the ambitious/narcissistic personality style in the "Personality Style and Disorders Inventory (PSSI)" (primary outcome) was improved (medium effect size: d=-0.49 [-0.67; -0.31], p<0.001). Analyses revealed even high effect sizes in terms of the improvement of depressive "states" and "traits", neuroticism as well as self-acceptance. The lowest effect sizes however were found for improvements in self-regulation (d=0.2 [0.03; 0.36], p=0.02). DISCUSSION: As no intention-to-treat analysis has been carried out, the effect sizes of COP in the treatment of NPS might be overestimated. Nevertheless, our findings support the use of COP for the treatment of NPS. In light of evidence-based medicine, the present so far most comprehensive study on this topic warranted an increase of the evidence of COP in the treatment of NPS from level IV to level III.

[Comparative Harm/Benefit Analysis of Various Psychotropic Substances from the Perspective of German Drug Users and Addiction Medicine Experts - A Contribution to Psychoeducation of Substance-Addicted Individuals and Restriction/Legalization Debates]. / Vergleichende Risiko/Nutzen-Analyse verschiedener psychotroper Substanzen aus der Perspektive deutscher Drogenkonsumenten und Suchtmediziner ­ Ein Beitrag für die Psychoedukationsarbeit mit Abhängigkeitserkrankten und Restriktions-/Legalisierungsdebatten.

BACKGROUND: To date, we cannot find any current international comparative study on the assessment of a benefit/harm profile of various licit and illicit psychoactive substances conducted by adult drug users and addiction experts as well. Particularly, there is no study from the German-speaking area of Western Europe. METHODS: In addition to the data already published by 101 German addiction medicine experts (published in this journal, [1]), we carried out interviews using a structured questionnaire with 100 German substance dependent users, residing in acute and rehabilitation clinical setting, to evaluate 34 psychoactive substances regarding their health and social harm potential for users and others as well as their potential benefit. RESULTS: Both, users and experts estimated traditional illicit drugs, such as heroin, crack/cocaine and methamphetamine, to be particularly harmful. Synthetic cannabinoids, alcohol and benzodiazepines were in the upper midfield, cannabis and psychotropic mushrooms in the lower midfield, and gabapentinoids at the bottom of the harm rankings of both, users and experts. In comparison with the experts, the users estimated methadone and benzodiazepines to be significantly more harmful. In the benefit analysis, users rated traditional illicit drugs including cannabis and psychotropic mushrooms as well as nicotine as significantly more useful than the experts. In contrast to the experts (traditional illicit drugs), the users did not assess any substance as very harmful and very useless at the same time. Only a few users reported to have experiences with opioid analgesics which, however, did not differ between the users´ and experts´ harm/benefit-assessments. Neither users nor experts predicted cannabis-legalization to change the overall risk potential of cannabis. Specific cognitive valuation biases seemed to be prominent in both groups. CONCLUSION: This study presents first harm/benefit assessments of psychotropic substances from the perspective of German addiction medicine experts and drug users. The results can be valuable to the psychoeducation of substance-addicted individuals and to current restriction or legalization debates.

[Weighing the benefits and harms of psychotropic and analgesic substances - A perspective of German addiction medicine experts]. / Abwägung von Nutzen und Schädlichkeit von berauschenden und schmerzlindernden Substanzen aus der Perspektive von deutschen Suchtmedizinern.

BACKGROUND: In Europe, there have been several addiction-expert rankings of harms related to the use of psychotropic substances in the last 15 years. Among them, only one expert ranking took into account the potential benefits of these drugs. Non-Opioidergic Analgesics (NOAs), such as gabapentinoids and NSAIDs, which have been increasingly the subject of abuse / misuse reports, have not been considered in such expert rankings. Likewise, there is currently no multi-substance comparison as to whether the valuation rank of the harmfulness of an illegal drug may change along with an imagined change in legal status in Germany. OBJECTIVES AND METHODS: Using a questionnaire, 101 experienced addiction physicians (first cohort) evaluated 33 psychoactive substances including analgesics with regard to their health and social harms as well as potential usefulness for the consumer and their environment / society ('others'). In addition, this cohort investigated whether the harmfulness assessment of an illegal substance changes if it would be legalized. In order to obtain the average overall harmfulness (overall risk) of a substance, the percentage contribution of each dimension to the overall harmfulness was determined in a second survey (second cohort, 36 experienced addiction medicine experts). Finally, the average benefit and overall risk ratings of each substance were related to each other. RESULTS: Prescription psychoactive substances such as analgesics, NOAs (including gabapentinoids) and opioidergic maintenance medications to treat opiate dependence were judged to have a favorable benefit-harm profile. Cannabis and ketamine were placed in the midfield of both, the harm and benefit rankings. Together with most illicit narcotic drugs, alcohol and nicotine, have been ranked among the most harmful and least useful substances, whereby alcohol was judged on average to be more harmful but also more useful than nicotine. In the event of potential legalization, the overall harm of the traditional illegal drugs methamphetamine, heroin, cocaine and cannabis was estimated to be reduced. This was mainly due to a more favorable valuation of the harm to others under these virtual conditions. CONCLUSION: Prescription substances including opioidergic and non-opioidergic analgesics as well as opioid maintenance therapy medications (methadone and buprenorphine) were assigned a favorable benefit-harm profile. Alcohol, nicotine and traditional illicit drugs (with the exception of cannabis and ketamine) were determined to have an unfavorable profile. The overall harm of traditional illicit drugs was assessed to decrease along with legalization, mainly by decreasing the harm to others in this virtual event.

Do patients' resilience and subjective illness representation predict the outcome of a routine inpatient treatment program of major depressive disorder?

Adopting a personalized medicine approach beyond genetic/epigenetic profiling within psychiatric diagnostic and treatment is challenging. For the first time, we studied the influence of two patient resources (resilience and illness representation) on the success of an inpatient treatment of major depressive disorder (MDD). Using a 5-week observational real-world-study, the treatment- success was measured by the difference between the subjective depression- severity (according to the German short form of Beck's Depression-Inventory) at baseline (i.e., days four to six post-admission) and study- endpoint. In the intention-to-treat sample (n = 60, 47.3 ± 12.8 years old; 58% females), the patients' illness representation [measured by the "Krankheitskonzeptskala" (KK)] did not predict their treatment- success. The KK-dimension 'trust-in-doctors' was associated with resilience but not with the treatment-success. Albeit, the patients' resilience (determined by Resilience- Scale, 11-item-version (RS-11)) negatively predicted their positive treatment- success (b = - 0.09, p = 0.017, f2 = 0.11). This influence of resilience on treatment- success was completely mediated by the baseline-depression- severity. This means, patients with low resilience reported high baseline-depression- levels which predicted a significant positive treatment- success. And, patients with high resilience reported low baseline-depression-levels which predicted no relevant or even negative inpatient treatment-success. The latter "high-resilience"- group (n = 27) was especially interesting. Remarkably, these patients appeared to have experienced within the first four-to-six inpatient treatment-days an "early sudden gain" against their considerable MDD- burden that initially had led to their admission. Thus, a stronger resilience might serve as a proxy of the development of an early MDD-relief as well as of lower baseline-depression- levels. Further studies are warranted to support the value of a patient's resilience to predict his treatment response and inpatient treatment duration.

Opioid painkiller dependence in a sample of elderly medical inpatients.

BACKGROUND: Over the past few years, there has been a growing concern about prescription opioid misuse and dependence in the elderly. Our study aimed to investigate the prevalence of previous and current prescription opioid dependence among elderly medical inpatients recruited from a large German hospital. METHODS: This cross-sectional study analyzed a cohort of inpatients aged 65 years and older who were assessed with a structured clinical interview. Levels of past and current dependence on opioids benzodiazepines, hypnotics, and non-opioid analgesics were assessed. RESULTS: Of 2108 elderly inpatients admitted to the hospital during a 6-month period, 400 fulfilled the inclusion criteria and agreed to participate to the survey. Among these 400 subjects, 43 (10.8%) presented with a dependence on opioid analgesics, including 41 with current dependence and 22 (51.2%) with a de novo condition. Addiction severity was considered mild in 65.1% of cases and severe in 11.6% of cases. Tilidine and oxycodone were the most typically reported molecules. CONCLUSIONS: Further research is warranted, to better understand the possible risk factors of prescription drug misuse, abuse, and addiction in this vulnerable population. Clinicians should be updated and informed regarding both prescription medication misuse potential and safe prescribing practices in the elderly.

Very Low Frequency of Drug Therapy of Alcohol Dependence in Germany - Analysis of Data of A Statutory Health Insurance.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

[A short essay on the spirituality of placebo from an (evolutionary) psychiatric perspective]. / Ein kurzes Essay über die Spiritualität von Placebo aus (evolutionär) psychiatrischer Sicht.

Different to spirituality, the placebo-effect is well operationalized. Against this background, an attempt is made to look at a possible phenomenological relationship between the therapeutic effectiveness of spirituality and placebo. Similar context influences as well as the possible common use of a phylogenetically well conserved protective route via the mesolimbic dopaminergic reward system are highlighted. For both phenomena, the clinical effectiveness seems to be ubiquitous, with that of the placebo effect being scientifically much more verified than this currently would be methodologically possible with the "spirituality effect". Both effects share their uncertain predictability and are Janus-headed (e. g., placebo effect vs. nocebo effect). Currently, for both, the placebo and spirituality-oriented approaches, there are attempts underway to maximize their clinical effectiveness by modulating the therapeutic framework and conversational content. The discussion ends with the reflexive question of whether the placebo effect could have in essence "spirituality-light" traits.

Aging is associated with a mild acidification in neocortical human neurons in vitro.

The intracellular pH (pHi) in the cytosol of mammalian central neurons is tightly regulated and small pHi-fluctuations are deemed to modulate inter-/intracellular signaling, excitability, and synaptic plasticity. The resting pHi of young rodent hippocampal pyramidal neurons is known to decrease alongside aging for about 0.1 pH-units. There is no information about the relationship between age and pHi of human central neurons. We addressed this knowledge gap using 26 neocortical slices from 12 patients (1-56-years-old) who had undergone epilepsy surgery. For fluorometric recordings, the slice-neurons were loaded with the pHi-sensitive dye BCECF-AM. We found that the pyramidal cells' resting pHi (n = 26) descended linearly alongside aging (r = - 0.71, p < 0.001). This negative relationship persisted, when the sample was confined to specific brain regions (i.e., middle temporal gyrus, 23 neurons, r = - 0.68, p < 0.001) or pathologies (i.e., hippocampus sclerosis, 8 neurons, r = - 0.78, p = 0.02). Specifically, neurons (n = 9, pHi 7.25 ± 0.12) from young children (1.5 ± 0.46-years-old) were significantly more alkaline than neurons from adults (n = 17, 38.53 ± 12.38 years old, pHi 7.08 ± 0.07, p < 0.001). Although the samples were from patients with different pathologies the results were in line with those from the rodent hippocampal pyramidal neurons. Like a hormetin, the age-related mild pHi-decrease might contribute to neuroprotection, e.g., via limiting excitotoxicity. On the other hand, aging cortical neurons could become more vulnerable to metabolic overstress by a successive pHi-decrease. Certainly, its impact for the dynamics in short and long-term synaptic plasticity and, ultimately, learning and memory provides a challenge for further research.

Effectiveness of Psychoanalytic-Interactional Group Therapy vs. Behavioral Group Therapy in Routine Outpatient Treatment of Alcohol-Dependent Patients.

BACKGROUND: The cognitive behavioral therapy has been extensively investigated to assess relapse prevention rates in patients with alcohol dependence. In contrast, only little is known regarding the effectiveness of psychoanalytical psychotherapy in relapse prevention, although this treatment is widely used and especially so in Germany. The aim of this quasi-randomized study was to compare the effectiveness of these two group treatments' approaches under the condition of routine outpatient treatment in a non-university hospital. METHODS: After inpatient detoxification, patients with alcohol dependence were allocated either to combined behavioral intervention (CBI) or to psychoanalytic-interactional therapy (PIT). The group treatment was carried out weekly over a period of six months. Also, the clinical care package included both individual treatment sessions (e.g. every 4-6 weeks) and abstinence supporting medication. The main outcome criteria included retention rates and frequency of alcohol relapse. RESULTS: Some 215 patients (mean age 49.6 years [standard deviation, 10], 56.7% males, with a mean duration of alcohol dependence of 16.5 years [range: 1-50 years]) were included in the study. Overall, CBI clients showed a retention rate of 66.7%, compared to 81.8% for PIT clients (p =.008). An intention-to-treat analysis of alcohol relapses showed a significant difference between PIT and CBI groups (PIT: 33.6%; CBI: 49.5%; p =.018). There were no statistically significant differences between the 2 groups in terms of prescription rates of disulfiram, naltrexone or acamprosate. CONCLUSIONS: Notwithstanding the study limitations, PIT seemed here to be at least as effective as CBI in terms of retention and relapse prevention rates' levels.

[On the risk of dependence on gabapentinoids]. / Über das Abhängigkeitspotential von Gabapentinoiden.

In the last ten years, the prescriptions of the gabapentinoids gabapentin and pregabalin increased largely also in Germany. Since several national and international pharmacovigilance-databases have warned for abuse liabilities and overdose fatalities in association with both gabapentinoids, which moreover, became to be sold on internet and black-markets, their addictive power has been subject to an ongoing clinical debate. As pre- and post-approval clinical trials did not reveal significant signs of dependence on gabapentin or pregabalin, we systematically searched in PubMed and Scopus for clinical studies and case reports being associated with abuse of and dependence on these drugs. We found 14 clinical-epidemiologic studies and 38 case reports/series. These were evaluated for i) fulfilled dependence criteria according to ICD-10, ii) non-medical self-administration and their duration, iii) relapses, iv) social sequels, and v) cases seeking treatment for misusing gabapentin or pregabalin. Mostly, the cases of abuse of and dependence on gabapentinoids appeared to be associated with other substance dependencies, primarily opiate dependence and polyvalent drug use. Drug users preferred pregabalin citing a faster and stronger euphoria ("liking") than achievable with oral gabapentin. Both gabapentinoids were anxiolytic in therapeutic doses, stimulating in lower and sedating along with increasing doses. Fatalities have been described mainly in the population of opiate dependents and polyvalent drug users, predominantly together with excessive pregabalin overdosing. It is debated whether the gabapentinoids were indeed the main cause of death in these cases or whether gabapentin and pregabalin had been only bystanders. Tolerance and withdrawal symptoms (physical dependence) of gabapentinoids appeared to be common in medical and non-medical use of gabapentinoids. There were only 4 persons who had fulfilled behavioral dependence criteria of gabapentinoids (all had used pregabalin) and had no association with other substance use disorders (apart from nicotine). Regarding the transitions from prescription to non-medical self-administration, the frequency and duration of self-administrations as well as the number of reported relapses, pregabalin appeared also to be more addictive than gabapentin. However, all these events were reported rather infrequently compared with traditional substances of abuse. We did not find a case with social sequalea due to the use of gabapentinoids or a person who sought treatment for his gabapentin or pregabalin use. Therefore, the gabapentinoids were assumed to possess a lower "wanting" in consideration of Berridge's and Robinsons's incentive-sensitization theory of addiction. Also, anti-adverse selection of gabapentinoids is discussed to be present in the population of opioid and multi-drug users. Based upon all these results and assumptions, we have estimated the relative risk of dependence on gabapentinoids by using an algorithm which was previously developed by Griffith and Johnson for evaluation of the abuse liabilities of sedatives. Overall, the risk of harm and dependence on gabapentinoids appeared to be lower than that of other sedatives (and stimulants). In addition, pregabalin appeared to be somewhat riskier than gabapentin. We think that in patients with current or past substance use disorders, the treatment with gabapentinoids should be avoided or if indispensable, these drugs should be administered exclusively over a limited time span with caution by using a therapeutic and prescription monitoring.