Kratom as an opioid alternative: harm, or harm reduction? A systematic review of literature.

Background: Kratom (Mitragyna speciosa Korth.) products are increasingly endorsed for self-management of multiple ailments, including as opioid substitution. The FDA has expressed that there is no evidence to indicate that this botanical is safe or effective for any medical use.Objective: We systematically review the current state of the literature concerning the impact of kratom and its alkaloids in all paradigms that involve opioids.Methods: A keyword search of online literature databases identified 16 preclinical studies, 25 case reports, and 10 observational studies meeting our pre-selected criteria.Results: All rodent models support alkaloids' action on opioid receptors, translating in their ability to mitigate opioid withdrawal. Some studies found mitragynine (MG) to have less reinforcing properties than morphine, and possessing tolerance-sparing properties when coadministered with morphine. Two studies that assessed 7-hydroxymitragynine (7OHMG) found it to substitute for morphine with potential for tolerance and dependence. Aside from addiction development, case reports outline a variety of confounding toxicities. Ten surveys of users, some conducted with assistance from pro-kratom lobbying organizations, find a high self-reported efficacy as an opioid substitute, with minimal reported adverse effects.Conclusion: With no reported controlled human clinical trials, in the light of rising concerns surrounding kratom's liabilities, there is insufficient evidence to allow any conclusions to be drawn. Case reports and observational studies carry significant bias toward harm and efficacy, respectively. Existing animal studies are heterogeneous in methodology and ultimately findings, with concern for interspecies variability and human translatability. Further research should investigate the safety and efficacy of using kratom alkaloids as opioid substitutes.

Catatonia in the medically ill: Etiology, diagnosis, and treatment. The Academy of Consultation-Liaison Psychiatry Evidence-Based Medicine Subcommittee Monograph.

BACKGROUND: Catatonia in medically ill patients is rare but often unrecognized. This monograph summarizes current knowledge on the diagnosis, epidemiology, etiology, and management of catatonia occurring in the medical setting. METHODS: PubMed searches were used to identify relevant articles from 1962 to present. RESULTS: More than 3,000 articles were obtained and reviewed for relevance, including references of articles identified by the initial search. Several areas were identified as important, including: (1) catatonia and delirium; (2) malignant catatonia; (3) pediatric catatonia; (4) catatonia associated with another medical condition (CAMC); (5) drug exposure and withdrawal syndromes associated with catatonia; and (6) treatment of catatonia in the medical setting. CONCLUSIONS: Catatonia in the medically ill appears to have numerous etiologies, although etiology does not seem to modify the general treatment approach of prompt administration of lorazepam. Delirium and catatonia are commonly comorbid in the medical setting and should not be viewed as mutually exclusive. Electroconvulsive therapy should be offered to patients who do not respond to benzodiazepines or have malignant features. Removing offending agents and treating the underlying medical condition is paramount when treating CAMC. Memantine or amantadine may be helpful adjunctive agents. There is not enough evidence to support the use of antipsychotics or stimulants in treating CAMC.

Recreational use of dextromethorphan, "Robotripping"-A brief review.

BACKGROUND: Dextromethorphan (DXM) in combination with antihistamines and/or pseudoephedrine is widely available as an over-the counter remedy commonly used for relief of colds and cough. In supra-therapeutic amounts, DXM has psychoactive effects. These cough preparations have been adopted by many young users of recreational drugs for these effects. OBJECTIVES: This paper aims to highlight the increasingly prevalent practice of Robotripping, review pharmacokinetic and dynamic data and discuss potential tolerance and withdrawal from the substance as well as treatment modalities. METHODS: A Medline search (1985-2015) for literature concerning the DXM was conducted. This was supplemented by references gleaned from recent epidemiological surveys and credible online sources to ensure most up to date information is gathered. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Use in amounts exceeding those recommended, a practice known as "Robotripping", may result in a toxidrome of psychomotor agitation, hallucinations and paranoia best characterized as Intoxication Delirium. Increasing misuse places greater numbers at risk. Providers should be alert to such presentations and be aware of methods for managing the symptoms. With chronic use, tolerance and withdrawal has been noted along with prolonging psychiatric sequelae. (Am J Addict 2016;25:374-377).

Electroconvulsive therapy improves persistent psychosis after repeated use of methylenedioxypyrovalerone ("bath salts").

The use of synthetic cathinone drugs, known popularly as "bath salts," may lead to persistent visual hallucinations and paranoia with repeated use. This is the first case report known to the authors suggesting that such symptoms may persist despite discontinuing the use of psychoactive bath salts. As is the case with other such symptoms associated with use of stimulant drugs of abuse, these symptoms are resistant to pharmacologic treatment, and electroconvulsive therapy can be a useful treatment modality in such situations. This report adds to evidence for efficacy of electroconvulsive therapy in the management of stimulant-induced persistent psychotic symptoms.

Intoxication delirium following use of synthetic cathinone derivatives.

BACKGROUND: In published reports of hallucinatory delirium following use of "bath salts" analytic laboratory testing has demonstrated the synthetic cathinone derivative methylenedioxypyrovalerone (MDPV). MDPV can cause a false-positive screening immunoassay result for phencyclidine (PCP). Patients using MDPV are prone to development of the syndrome of excited delirium (ExD), a condition also described with PCP. OBJECTIVE: This review summarize reports from several series of cases of delirium associated with MDPV emphasizing the features of both intoxication and excited delirium. METHODS: Literature review and clinical description of a series of patients from Eastern North Carolina. CONCLUSION: MDPV is likely the responsible agent in production of both toxic and excited delirium syndromes identified with the recreational use of "bath salts" in the United States over the past two years. SCIENTIFIC SIGNIFICANCE: Patients using MDPV are prone to the development of toxic delirum with some developing ExD. a condition associated with considerable risk for serious medical morbidity. Commonly used interventions directed at extreme agitation and paranoia may exacerbate the pathophysiology of ExD.

Pharmacotherapy for Management of 'Kratom Use Disorder': A Systematic Literature Review With Survey of Experts.

OBJECTIVES: An increasing number of Americans are turning to kratom for self-management of various pain, anxiety, and mood states and as an opioid substitute. Addiction to this unique botanical develops and carries a high relapse risk and, to date, there are no guidelines on how to maintain long-term abstinence. The aim of this article is to compile all available information on management of "kratom use disorder" (KUD)-as coined here-from the literature, with evidence from the clinical practice of expert addictionologists in an attempt to develop a standard of care consensus. METHODS: A systematic literature search was conducted to capture all relevant cases pertaining to maintenance treatment for KUD. Results were supplemented with case reports and scientific posters gleaned from reliable online sources and conference proceedings. Additionally, a survey of members of the American Society of Addiction Medicine (ASAM) was administered to assess the practice patterns of experts who treat patients with KUD in isolation of a comorbid opioid use disorder (OUD). RESULTS: Based on a literature review, 14 reports exist of long-term management of KUD, half of which do not involve a comorbid OUD. Pharmacological modalities utilized include mostly buprenorphine but also a few cases of naltrexone and methadone, all with favorable outcomes. This is supported by the results of the expert survey, which demonstrated that those who have managed KUD in isolation of a comorbid OUD reported having utilized buprenorphine (89.5%), as well as the other medications for opioid use disorder (MOUD). CONCLUSIONS: This is the first comprehensive review to examine the existing literature referring to management of KUD in combination with a survey of current experts' clinical consensus regarding pharmacological management. Based on this information, it seems reasonable that the indication for MOUD should be extended to cases of moderate to severe KUD.

Kratom Withdrawal: A Systematic Review with Case Series.

Recent years have seen a widespread increase in kratom use, not just for the purpose of easing opioid withdrawal, but also for management of emotional and mental health concerns by individuals without histories of opioid use. Chronic use can lead to dependence, tolerance, and withdrawal on cessation, and clinicians are seeing an increasing number of presentations involving the latter. Although there is literature discussing the use of kratom to assist in opioid withdrawal, this article comprehensively examines independent withdrawal from kratom. We systematically review existing evidence and provide our own clinical cases. Clinicians need to be aware of the withdrawal symptomatology and implement a similar approach as for opioid withdrawal with long-term maintenance to prevent relapse.

Use of Buprenorphine in treatment of refractory depression-A review of current literature.

OBJECTIVE: Current treatment strategies for depressive disorders have limited efficacy, leaving many patients unimproved or with significant residual symptoms. The development of additional treatments represent a significant unmet need for providers. Several lines of evidence suggest that the opioid system may be involved in regulation of mood and incentives salience. Intervention based on modifying central opioid receptors may represent a novel approach to treatment of depressive disorders among those unresponsive to accepted treatments. DATA SOURCES: We searched the English language literature using keywords: Buprenorphine AND Major Depression; Buprenorphine AND Bipolar Depression; Buprenorphine AND Affective Disorders. RESULTS: Use of low dose buprenorphine as augmentation of pharmacotherapy for depression has shown promise in several reported studies. Effect size of available randomized controlled studies is comparable if not greater than most accepted augmentation strategies. CONCLUSION: Review of available literature on the use of buprenorphine in individuals with treatment resistant depression demonstrated efficacy in the treatment of depressive disorders. Further prospective randomized controlled trials should be undertaken to evaluate the efficacy of buprenorphine as an adjunct for depression refractory to current pharmacotherapies.

eMindLog: Self-Measurement of Anxiety and Depression Using Mobile Technology.

BACKGROUND: Quantifying anxiety and depressive experiences permits individuals to calibrate where they are and monitor intervention-associated changes. eMindLog is a novel self-report measure for anxiety and depression that is grounded in psychology with an organizing structure based on neuroscience. OBJECTIVE: Our aim was to explore the psychometric properties of eMindLog in a nonclinical sample of subjects. METHODS: In a cross-sectional study of eMindLog, a convenience sample of 198 adults provided informed consent and completed eMindLog and the Hospital Anxiety and Depression Scale (HADS) as a reference. Brain systems (eg, negative and positive valence systems, cognitive systems) and their functional states that drive behavior are measured daily as emotions, thoughts, and behaviors. Associated symptoms, quality of life, and functioning are assessed weekly. eMindLog offers ease of use and expediency, using mobile technology across multiple platforms, with dashboard reporting of scores. It enhances precision by providing distinct, nonoverlapping description of terms, and accuracy through guidance for scoring severity. RESULTS: eMindLog daily total score had a Cronbach alpha of .94. Pearson correlation coefficient for eMindLog indexes for anxiety and sadness/anhedonia were r=.66 (P<.001) and r=.62 (P<.001) contrasted with the HADS anxiety and depression subscales respectively. Of 195 subjects, 23 (11.8%) had cross-sectional symptoms above the threshold for Generalized Anxiety Disorder and 29 (29/195, 14.9%) for Major Depressive Disorder. Factor analysis supported the theoretically derived index derivatives for anxiety, anger, sadness, and anhedonia. CONCLUSIONS: eMindLog is a novel self-measurement tool to measure anxiety and depression, demonstrating excellent reliability and strong validity in a nonclinical population. Further studies in clinical populations are necessary for fuller validation of its psychometric properties. Self-measurement of anxiety and depressive symptoms with precision and accuracy has several potential benefits, including case detection, tracking change over time, efficacy assessment of interventions, and exploration of potential biomarkers.

Withdrawn: The Behavioral Profile of methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (PVP) - A Systematic Review.

The article entitled, "The Behavioral Profile of Methylenedioxypyrovalerone (MDPV) and α­ pyrrolidinopentiophenone (PVP) - A Systematic Review", submitted in Current Drug Abuse Reviews (CDAR) by Dr. Cornel N Stanciu has been withdrawn from the journal in accordance with BSP Editorial Policies.

Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis.

BACKGROUND: Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy. DATA SOURCES: We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder. STUDY SELECTION AND DATA EXTRACTION: Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy ≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis. RESULTS: Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5. CONCLUSIONS: Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy ≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern.

Mania after misuse of dextromethorphan: a case report and brief review of "robotripping".

Dextromethorphan (DXM) in combination with antihistamines and/or pseudoephedrine is widely available as an over-the-counter remedy commonly used for relief of colds and cough. In supratherapeutic amounts, DXM can be extremely activating. These cough preparations have been adopted by many young users of recreational drugs for their psychoactive effects. When used in amounts exceeding those recommended, this practice, known as "robotripping," may result in a manic toxidrome of psychomotor agitation, hostility, grandiose behavior, hallucinations, paranoia, and panic. A case illustration of this phenomenon is described and implications of this phenomenon discussed. There are few reports associating DXM use with bipolar symptomatology.

Psychogenic polydipsia, hyponatremia and osmotic myelinolysis.

OBJECTIVE: Description of a case of osmotic myelinolysis associated with hyponatremia produced as a consequence of compulsive water drinking. METHOD: Case report and review of relevant literature. RESULTS: Compulsive water drinking or psychogenic polydipsia is a common cause of hyponatremia among individuals with chronic mental illness. Central pontine myelinolysis and extrapontine myelinolysis are serious neurological complications resulting from rapid correction of serum sodium and associated changes in serum osmolality. A case of extrapontine myelinolysis confirmed by characteristic MRI findings following an episode of extreme hyponatremia caused by psychogenic polydipsia is described involving a patient with an adult lifelong history of chronic mental illness diagnosed as schizoaffective disorder. With supportive care the related cognitive deficits and balance difficulties resolved completely. CONCLUSIONS: Clinicians should be aware of the potential for hyponatremia resulting from compulsive water drinking to cause myelinolysis with delayed development of cognitive and gait symptoms that responds to supportive care if identified early.

Persistent akathisia masquerading as agitated depression after use of ziprasidone in the treatment of bipolar depression.

There has been increasing recognition that the second-generation antipsychotic drugs can produce extrapyramidal side effects. This case reports the development of severe akathisia in a patient being treated with ziprasidone for bipolar depression. The case illustrates that this symptom can be easily mistaken for worsening agitated depression. Akathisia may produce considerable distress and elevate suicide risk. Such symptoms may persist for weeks and be refractory to discontinuation of the offending agent or to pharmacological interventions commonly used to mitigate this reaction.

Excited delirium following use of synthetic cathinones (bath salts).

Synthetic analogs of the cathinone molecule have seen increasing recreational use as substitutes for cocaine, 3,4-methylenedioxymethamphetamine (ecstasy) and methamphetamine. Repeated use of these drugs is associated with a paranoid hallucinatory delirium. A subset of patients using these substances develops a syndrome of extreme agitation and violent behavior that has been reported following the use of other stimulant drugs that also produce rapid changes in brain monoamines. This syndrome, characterized as "excited delirium," presents to the acute care setting with a challenging combination of paranoia, severe agitation and violent behavior. These patients frequently suffer from dehydration, skeletal muscle damage and renal failure that may lead to multiorgan failure and death. Management of these individuals requires careful consideration of the consequences of interventions commonly implemented in medical settings to control dangerous aggressive behavior.