[Stopping antidepressants: withdrawal symptoms and rebound effects : Review and practical recommendations]. / Absetzen von Antidepressiva ­ Absetzsymptome und Rebound-Effekte : Übersicht und praktische Empfehlungen.

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

[Neurobiology of opioid dependence]. / Neurobiologie der Opioidabhängigkeit.

Opioid dependence is a chronic mental disease with multifactorial etiology. The neurobiological theory of addiction focuses on the manipulation of the dopaminergic reward system as a basic property of substances with addictive potential including opioids. With regular opioid intake, the manipulation of the reward system results in a cognitive bias towards drug-related stimuli. In addition, opioids inhibit the locus caeruleus, resulting in symptoms of sympathetic rebound during opioid detoxification. The pharmacokinetics of opioids also influence the risk of addiction. These biological factors are independent of the legal status of the individual opioid. Genetics also significantly influence the etiology. However, the assignment of this genetic influence is difficult because not only basic biological functions, but also personality traits and mental illnesses are genetically determined.

Outcome of a hepatitis B vaccination program for clients of a drug consumption facility.

BACKGROUND: Intravenous drug users (IDUs) are a risk group for hepatitis B. In Germany, the hepatitis B virus (HBV) vaccination rates in IDUs are low. OBJECTIVES: In this study the implementation and success of HBV vaccination in a drug consumption facility (DCF) was evaluated. STUDY DESIGN: Clients attending a DCF were asked regarding their HBV status. In case of no known HBV infection and no previous vaccination, clients interested in HBV vaccination were offered a HBV blood testing. HBV vaccination was administered to susceptible clients in months 0, 1, 6. Booster vaccinations were offered to clients without seroconversion (anti-HBs < 100 U/l). RESULTS: 193 out of 364 clients reported on a known HBV infection or immunity after vaccination. 95 (55.6%) out of 171 eligible clients underwent a HBV serology. According to HBV serology 31 (32.6%) out of 95 clients were not susceptible for vaccination (mainly due to an unknown HBV infection). 47 (73.4%) out of 64 clients susceptible were administered 3 vaccinations. 10 clients received at least one further vaccination. For those showing up for testing (36 out of 47 clients) the seroconversion rate was 69.4% (> 100 IU/l) and 83.3% (> 10 IU/l), respectively. DISCUSSION: Only a minority of clients of a DCF was susceptible for HBV vaccination. 47 out of 64 (73.4%) susceptible clients underwent at least three administrations of the vaccine, mostly resulting in seroconversion. Even in IDUs attending a DCF, a clientele with unstable social and health conditions, HBV vaccination can be carried out successfully.

[Neurobiology of opioid dependence]. / Neurobiologie der Opioidabhängigkeit.

Opioid dependence is a chronic mental disease with multifactorial etiology. The neurobiological theory of addiction focuses on the manipulation of the dopaminergic reward system as a basic property of substances with addictive potential including opioids. With regular opioid intake, the manipulation of the reward system results in a cognitive bias towards drug-related stimuli. In addition, opioids inhibit the locus caeruleus, resulting in symptoms of sympathetic rebound during opioid detoxification. The pharmacokinetics of opioids also influence the risk of addiction. These biological factors are independent of the legal status of the individual opioid. Genetics also significantly influence the etiology. However, the assignment of this genetic influence is difficult because not only basic biological functions, but also personality traits and mental illnesses are genetically determined.

How addictive are gabapentin and pregabalin? A systematic review.

In the last ten years, gabapentin and pregabalin have been becoming dispensed broadly and sold on black markets, thereby, exposing millions to potential side-effects. Meanwhile, several pharmacovigilance-databases have warned for potential abuse liabilities and overdose fatalities in association with both gabapentinoids. To evaluate their addiction risk in more detail, we conducted a systematic review on PubMed/Scopus and included 106 studies. We did not find convincing evidence of a vigorous addictive power of gabapentinoids which is primarily suggested from their limited rewarding properties, marginal notes on relapses, and the very few cases with gabapentinoid-related behavioral dependence symptoms (ICD-10) in patients without a prior abuse history (N=4). In support, there was no publication about people who sought treatment for the use of gabapentinoids. Pregabalin appeared to be somewhat more addictive than gabapentin regarding the magnitude of behavioral dependence symptoms, transitions from prescription to self-administration, and the durability of the self-administrations. The principal population at risk for addiction of gabapentinoids consists of patients with other current or past substance use disorders (SUD), mostly opioid and multi-drug users, who preferred pregabalin. Pure overdoses of gabapentinoids appeared to be relative safe but can become lethal (pregabalin > gabapentin) in mixture with other psychoactive drugs, especially opioids again and sedatives. Based upon these results, we compared the addiction risks of gabapentin and pregabalin with those of traditional psychoactive substances and recommend that in patients with a history of SUD, gabapentinoids should be avoided or if indispensable, administered with caution by using a strict therapeutic and prescription monitoring.

[Outcome Quality of Open General Psychiatric Inpatient Treatment at the Meso Level - an Observational Study in an Urban German General Hospital]. / Zur Ergebnisqualität der allgemeinpsychiatrischen offenstationären Krankenhausbehandlung auf der Mesoebene - eine prospektive Studie aus einem urbanen Allgemeinkrankenhaus.

BACKGROUND: Inpatient treatment (meso level) in psychiatric hospitals is commonly assumed to be effective. However, there is very little evidence-based data on this issue. OBJECTIVES AND METHODS: First evaluation of the outcome quality of an inpatient general psychiatric treatment in a German general hospital using multifaceted quality indicators (symptom severity, wellbeing, self-efficacy, depressive avoidance, patients' satisfaction with the treatment) was carried out. Patients with a wide range of psychiatric diagnoses (ICD-10 F2-F6) were randomly assigned to this naturalistic single-group pre-post study. For ethical and methodological reasons, only adult inpatients treated in open general psychiatric wards were enrolled. RESULTS: The sample (n = 110, 58.2 % females) had a mean age of 47.2 (SD 15.9) years. 67 (60.9 %) and 29 (26.4 %) patients had at least one or two additional psychiatric diagnoses, respectively. 84 (76.4 %) and 62 (56.4 %) patients had a minimum of one or two additional somatic diagnoses, respectively. The treatment lasted 38 (SD 36; median 28.5) days. Significant positive treatment effects for all quality indicators were found at regular hospital discharge. The effect sizes varied between Cohen's d = 0.17 - 0.62 ("intention-to-treat" population, n = 110) and d = 0.28 - 0.99 ("completer" population, n = 70). DISCUSSION AND CONCLUSION: This study provides direct evidence for the effectiveness of an open inpatient general psychiatric hospital treatment at the meso level. The results, however, are not representative for all German general psychiatric wards because of major differences between hospitals in personnel resources and framework conditions.

Abrupt Quitting of Long-term Heavy Recreational Cannabis Use is Not Followed by Significant Changes in Blood Pressure and Heart Rate.

OBJECTIVE: To shed more light on the role of heart rate and blood pressure during cannabis withdrawal. METHODS: Post-hoc analysis of data collected during a prospective inpatient monitoring of withdrawal symptoms of 39 (8 female) adult (median 27 year old) treatment-seeking, predominantly white cannabis-dependents (Bonnet et al., Drug Alcohol Depend 2014; 143: 189-97). Beyond tobacco smoking, the body mass index, electrocardiogram and routine laboratory results were considered to estimate the cohort's risk for cardiovascular disease (CVD). RESULTS: Abrupt cessation of recreational long-term daily cannabis use was not followed by significant changes in heart rate, blood and pulse pressure. Also, these measures were not significantly correlated with the severity of the cannabis withdrawal syndrome. The cohort's risk for CVD was moderate (all tobacco using, overweight in 9 of 35 patients and elevation of serum C-reactive protein in many patients). Its metabolic risk for CVD was minor considering the mostly normal blood pressure, normal serum lipids and glucose. DISCUSSION: This merely minor metabolic risk might have contributed to the missing effects of cannabis cessation on the basic cardiovascular functions.

[Guideline-oriented treatment of alcohol-related disorders]. / Leitlinienorientierte Behandlung alkoholbezogener Störungen.

Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15% of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved.This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40% could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year.

[On the Differential Diagnosis of Intractable Psychogenic Chronic Cough: Neuropathic Larynx Irritable - Gabapentin's Antitussive Action]. / Zur Differenzialdiagnose des quälenden psychogenen chronischen Hustens: neuropathischer Larynx irritable - Gabapentin als Antitussivum.

We present the case of a 76 year old female inpatient who suffered from a chronic intractable cough which arose simultaneously to a severe major depression and was secondary to an exorbitant psychological distress. Chronic cough had never been experienced before and was initially considered to have a mere psychogenic origin since a comprehensive and guideline-based diagnostic screening did not reveal any underlying somatic cause. However, several factors cast doubt on the solitary psychic genesis of the chronic cough: i) occurrence immediately after a penetrant cold, ii) embedding in other complaints of laryngeal hyperreagibility (larynx irritable), such as persistent globus pharyngeus sensation, throat clearing and episodic dysphonia, iii) first occurrence on old life, iv) erupting from sleep as well, v) persistence despite remission of the major depression, and v) no sustaining benefit from specific psychotherapy and speech therapy. Therefore, diagnostics were extended to apparative tools for objective evaluation of swallowing by using fiberoptic videoendoscopic (FEES) and videofluoroscopic (VFS) techniques, which revealed signs of laryngeal neuropathy but without evidence of penetration or aspiration. A co-existing small goiter and an impaired glucose tolerance along with a putative intracellular vitamin B12 or folate deficiency (as indirectly derived from an apparent hyperhomocysteinemia) were assumed to be responsible for the neuropathy and underwent specific treatments. The impaired glucose tolerance and putative vitamin deficit were compatible with a distal symmetric sensorimotoric, even subclinical polyneuropathy of the lower extremities. The larynx irritable improved under gabapentin being confirmed by drug removals several times, and finally calmed down almost completely under gabapentin, which was in line with the scant literature of this topic. Re-examination of the larynx per FEES nine months later showed no deficits any more under the well-tolerated treatment (gabapentin, levothyroxine, vitamin B12 and folic acid substitution, weight reduction and physical training). All in all, the larynx irritable as well as the chronic cough were most probably induced by a laryngeal neuropathy and were not solely of psychic origin. Due to good treatment options a larynx irritable should be regularly taken into consideration of the investigation of intractable chronic cough. Therefore, an apparative evaluation of deglutition is recommended in the diagnostic toolbox of chronic cough - even if embedded in a psychiatric disorder or distress - before diagnosing a sole psychic origin. An hypothetical scheme of the development of a larynx irritable caused by neuropathic and non-neuropathic ("nociceptive") conditions is proposed.

[Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard]. / Synthetische Cannabinoide: Verbreitung, Suchtbiologie & aktuelle Perspektive der persönlichen Gesundheitsgefährdung.

Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e. g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e. g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs.

Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification: cannabis withdrawal syndrome and its correlation with delta-9-tetrahydrocannabinol and -metabolites in serum.

OBJECTIVE: To investigate the course of cannabis withdrawal syndrome (CWS) within a controlled inpatient detoxification setting and to correlate severity of CWS with the serum-levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). METHODS: Thirty-nine treatment-seeking chronic cannabis dependents (ICD-10) were studied on admission and on abstinent days 2, 4, 8 and 16, using a CWS-checklist (MWC) and the Clinical Global Impression-Severity scale (CGI-S). Simultaneously obtained serum was analysed to its concentration of THC, THC-OH and THC-COOH. RESULTS: MWC peaked on day 4 (10.4 ± 4.6 from 39 points) and declined to 2.9 ± 2.4 points on day 16. Women had a significantly stronger CWS than men. The CWS was dominated by craving>restlessness>nervousness>sleeplessness. CGI-S peaked with 5 out of 7 points. On admission, THC and its metabolites did negatively correlate with the severity of CWS. There was no significant correlation afterwards, no matter if CWS was medicated or not. THC-OH in serum declined most rapidly below detection limit, on median at day 4. At abstinence day 16, the THC-levels of 28.2% of the patients were still above 1g/ml (range: 1.3 to 6.4 ng/ml). CONCLUSIONS: CWS increased and then decreased without any correlation between its severity and the serum-levels of THC or its main metabolites after admission. According to the CGI-S, most patients achieved the condition of 'markedly ill'. Serum THC-OH was most clearly associated with recent cannabis use. Residual THC was found in the serum of almost one-third of the patients at abstinence day 16.

[No opiates against cannabis hyperemesis syndrome]. / Keine Opiate gegen das Cannabis-Hyperemesis-Syndrom.

HISTORY AND CLINICAL FINDINGS: An otherwise healthy 25-year-old patient with heavy cannabis-abuse suffered from an undiagnosed cannabis hyperemesis syndrome (CHS) over years, which characteristically was resistant to usual antiemetics. In an apparently last attempt at healing, opiates (morphine, methadone) were administrated and improved the CHS, however, this led to an at least as equally distressing and painful opiate withdrawal syndrome. TREATMENT AND COURSE: In the controlled cannabis abstinence during the 2-week inpatient treatment of opiate addiction syndrome the CHS has not recurred. CONCLUSION: Opiates are not suited for the treatment of CHS because they are addictive and lead to respiratory depression in overdose.

Acute bilateral parotitis occurring during venlafaxine titration in an adolescent female with major depression.

Parotitis is a fairly uncommon adverse drug reaction of psychopharmacological treatment. Here, we report on an acute bilateral parotitis, which was associated with titration of venlafaxine in a 20-year-old female suffering from a severe depressive episode. The parotitis recovered quickly with oral penicillin and was most likely caused by bacteria assumed to spread from oral flora into Stensen's duct as a complication of pronounced venlafaxine-induced xerostomia.

Chronic cannabis abuse, delta-9-tetrahydrocannabinol and thyroid function.

OBJECTIVE: The aim of this study was to obtain rather rare information about the influence of chronic cannabis abuse on thyroid function. METHODS: Thyroid function tests (TSH, total T3, free T4) of 39 chronic cannabis-dependent subjects (ICD-10) were determined at admission (for in-patient detoxification). In a subgroup, serum levels of thyroid hormones were correlated with the serum levels of delta-9-tetrahydrocannabinol (THC, N=24) and its major metabolites, THC-OH (N=16) and THC-COOH (N=24). RESULTS: All of the tested patients were found to have TSH, total T3 and free T4 levels within the population reference range. The levels of thyroid hormones did not correlate significantly with levels of THC, THC-OH or THC-COOH in serum. CONCLUSION: These results argue against a relevant influence of chronic cannabis intake on thyroid function in humans.

[Neuropsychopharmaca influence the intracellular pH value of central neurons]. / Neuropsychopharmaka verändern den intrazellulären pH-Wert von zentralen Neuronen.

The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound transporters acting as acid extruders or acid loaders. Regulation of pHi helps to control neuronal excitability, as increased bioelectric activity moderately lowers pHi and, in the sense of a negative feedback loop, intracellular acidosis mostly reduces neuronal excitability. Moreover, a change of pHi widely influences complex cellular functions. With respect to neuropsychopharmaca, little is known about whether or not they may affect neuronal H ( + )-homeostasis. To this aim, we tested several antipsychotics, antidepressants, anticonvulsants, and lithium for effects on neuronal pHi, using guinea pig hippocampal slice preparations in which CA 3 pyramidal neurons were loaded with the pHi-sensitive dye BCECF-AM. All antipsychotics, most antidepressants and about half of the anticonvulsants tested so far elicited reversible changes of neuronal pHi when applied at therapeutic and supratherapeutic concentrations. Although these results await confirmatory in vivo experiments, we believe that the pHi activity of neuropsychopharmaca needs further attention, especially when therapeutic mechanisms or even harmful side effects are discussed.

[Cannabis hyperemesis syndrome]. / Cannabis-Hyperemesis-Syndrom.

We present the course of cyclical hyperemesis most likely induced by cannabis in a young cannabis-dependent, but otherwise healthy female adult. Cyclical hyperemesis developed in parallel to increasing cannabis inhalation, and remitted completely within a few days of abstinence in a protective inpatient setting. Just as in those increasing cases which can be found in literature, the hyperemesis improved by taking a hot shower or bath at the beginning of the detoxification. This thermosensitivity, along with the detection of a central disturbance of the thyroid axis, points to the hypothalamic cannabinoid system being involved in cannabis-induced cyclical hyperemesis. The patient was followed up for 4 months without any re-occurrence of the syndrome during controlled cannabis abstinence.

[Assessment of the addictive risk of propofol]. / Einschätzung des Abhängigkeitsrisikos von Propofol.

In a survey of American and German medical personnel, the injectable hypnotic propofol was identified as one of the most frequently abused anaesthetics. With the help of MEDLINE, EMBASE, Scopus, Cochrane and internet search, data were sought that permit an assessment of propofol's risk of addiction. The clinical evaluation for hypnotics can usually be made with the scale of Griffith and Johnson. Thereafter, the relative risk of addiction (dependence potential/toxicity) of propofol is rather moderate if compared to phenobarbital. Its addictive potential is somewhat lower than that of lorazepam and cannabis (non-hypnotic reference) approximately in the range of that of triazolam or zopiclon. The few published clinical case reports (n = 8) are mainly from Germany and describe distinct psychological (craving, loss of control, focusing of behaviour on the use and procurement of the substance) and low levels of physical features of addiction (withdrawal symptoms, tolerance). On average, in the case reports 4.25 of 6 criteria of dependence (ICD-10) were met. The consumption of propofol is mainly limited to medical or medical-related occupations. Propofol has yet not arrived on the local black markets. An oral consumption appears not to occur or to be unattractive. The incentive of propofol's "high" (euphoria/relaxation) via the intravenous route is probably underestimated. This is supported by a high mortality rate (46.2 %) in the 78 reports on the consumption of propofol up to date. Forensic analyses consider mainly accidental respiratory arrests to be responsible for the deaths. In summary, propofol is considered to be a primary mental addictive substance that is characteristically intravenously consumed by persons within the medical profession. Because of its apparently narrow safety margin between pleasure and death, propofol is an extraordinary hazard which, unfortunately, is only reflected insufficiently in the scale of Griffith and Johnson.

Influence of the 393T>C polymorphism of the GNAS1 gene on the intensity of opiate withdrawal.

There are high interindividual differences regarding the intensity of withdrawal symptoms. in opiate addicts. This study was carried out in order to test whether the intensity of withdrawal is influenced by the 393T>C polymorphism of the GNASI gene. Only patients addicted exclusively to opiates were included. Thirty-three out of 39 patients undergoing inpatient detoxification treatment achieved a drug-free state. During the most intense period of withdrawal (stop of methadone and following days) TT homozygotes (n=4) had a significantly higher pulse rate (primary outcome criterion) than C-allele carriers (n=29). This study and a previous study about GNB3 825C> T underline the possible role of G-protein polymorphisms in the interindividual variability of opiate withdrawal.