Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

/pdf/consensus-guidelines-for-therapeutic-drug-monitoring-in-18b8y5mu39.pdf

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Background:The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines r...

https://journals.sagepub.com/doi/pdf/10.1177/0706743716659417

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder Section 3. Pharmacological Treatments

Objectives: To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. Methods: Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care.

/pdf/royal-australian-and-new-zealand-college-of-psychiatrists-29brj3xyri.pdf

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with reported prevalence in the United States of 1 in 59 children (approximately 1.7%). Core deficits are identified in 2 domains: social communication/interaction and restrictive, repetitive patterns of behavior. Children and youth with ASD have service needs in behavioral, educational, health, leisure, family support, and other areas. Standardized screening for ASD at 18 and 24 months of age with ongoing developmental surveillance continues to be recommended in primary care (although it may be performed in other settings), because ASD is common, can be diagnosed as young as 18 months of age, and has evidenced-based interventions that may improve function. More accurate and culturally sensitive screening approaches are needed. Primary care providers should be familiar with the diagnosticcriteria for ASD, appropriate etiologic evaluation, and co-occurring medical and behavioral conditions (such as disorders of sleep and feeding, gastrointestinal tract symptoms, obesity, seizures, attention-deficit/hyperactivity disorder, anxiety, and wandering) that affect the child’s function and quality of life. There is an increasing evidence base to support behavioral and other interventions to address specific skills and symptoms. Shared decision making calls for collaboration with families in evaluation and choice of interventions.  This single clinical report updates the 2007 American Academy of Pediatrics clinical reports on the evaluation and treatment of ASD in one publication with an online table of contents and section view available through the American Academy of Pediatrics Gateway to help the reader identify topic areas within the report.

Identification, Evaluation, and Management of Children With Autism Spectrum Disorder.

Background:The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals.Methods:Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Psychological Treatments” is the second of six sections of the 2016 guidelines.Results:Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their ef...

https://journals.sagepub.com/doi/pdf/10.1177/0706743716659418

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 2. Psychological Treatments

Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).

https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.147

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

Mr. S, a 45-year-old veteran, was diagnosed with posttraumatic stress disorder (PTSD) 18 years ago after a tour of duty in the Persian Gulf. He had combat-related flashbacks triggered by the smell of gasoline or smoke from a fire, was easily startled, and began to isolate himself socially. However, his symptoms improved when he started volunteering at his local Veterans Affairs Medical Center. After he lost his job 3 years ago, Mr. S started experiencing flashbacks. He was irritable, easily startled, and avoided things that reminded him of his time in the Persian Gulf. His psychiatrist prescribed sertraline, titrated to 200 mg/d. The drug reduced the severity of his avoidance and hyperarousal symptoms and improved his mood. [ILLUSTRATION OMITTED] During a clinic visit, Mr. S says he is doing well and can fall asleep at night but is having recurring nightmares about traumatic events that occurred during combat. These nightmares wake him up and have become more frequent, occurring once per night for the past month. Mr. S says he has been watching more news programs about conflicts in Afghanistan and Iraq since the nightmares began. His psychiatrist starts quetiapine, 50 mg at bedtime for 7 nights then 100 mg at bedtime, but after 6 weeks Mr. S says his nightmares continue. PTSD occurs in approximately 19% of Vietnam war combat veterans (1) and 14% of service members returning from Iraq and Afghanistan. (2) PTSD symptoms are classified into clusters: intrusive/re-experiencing; avoidant/numbing; and hyperarousal. (3) Nightmares are part of the intrusive/re-experiencing cluster, which is Criterion B in DSM-IV-TR. See this article at CurrentPsychiatry.com for a description of DSM-IV-TR PTSD criteria. Among PTSD patients, 50% to 70% report PTSD-associated nightmares. (4) Despite adequate treatment targeted to improve PTSD's core symptoms, symptoms such as sleep disturbances or nightmares often persist. Nightmares and other sleep disturbances are associated with significant distress and daytime impairment and can interfere with PTSD recovery (4-8) by disrupting sleep-dependent processing of emotional experiences and causing repeated resensitization to trauma cues (Table 1, page 60). (8) Few randomized controlled medication trials specifically address PTSD-related nightmares. Most PTSD studies do not examine sleep outcomes as a primary measure, and comprehensive literature reviews could not offer evidence-based recommendations. (9), (10) The American Academy of Sleep Medicine (AASM) also noted a paucity of PTSD studies that identified nightmares as a primary outcome measure." See this article at CurrentPsychia try.com for a list of recommended medication options for PTSD-associated nightmares. Table1 Psychosocial consequences of sleep disruption in PTSD Increased reactivity to emotional cues Compromised ability to function in social and occupational roles Negative psychiatric outcomes, including suicidal ideation or worsening of depression or psychosis Interference of natural recovery from trauma exposure Repeated resensitization to trauma cues Neurocognitive deficits Neuroendocrine abnormalities PTSD: posttraumatic stress disorder Source: Adapted from reference 8 CASE CONTINUED Medication change, improvement After reviewing AASM's treatment recommendations, we prescribe prazosin, 1 mg at bedtime for 7 nights, then increase by 1 mg at bedtime each week until Mr. S's nightmares improve. He reports a substantial improvement in nightmare severity and frequency after a few weeks of treatment with prazosin, 5 mg at bedtime. Prazosin Prazosin is an [alpha]l-adrenergic receptor antagonist with good CNS penetrability. The rationale for reducing adrenergic activity to address intrusive PTSD symptoms has been well documented. (12), (13) In open-label trials, (14-18) a chart review, (19) and placebo-controlled trials, (20-22) prazosin reduced trauma nightmares and improved sleep quality and global clinical status more than placebo (Table 2). …

PTSD Nightmares: Prazosin and Atypical Antipsychotics

Mr. C, age 31, who has a 7-year history of schizophrenia and is currently on perphenazine, 24 mg twice a day, presents for psychiatric admission after experiencing paranoid delusions. Notable symptoms include delusions of reference and persecution, along with affective flattening and intermittent suicidal ideation. Perphenazine is tapered, and he is started on quetiapine, titrated to 600 mg/d. Past antipsychotic trials include aripiprazole, olanzapine, paliperidone, haloperidol, and ziprasidone. Because of his refractory symptoms and tolerability issues with other antipsychotics, Mr. C is switched to clozapine, 400 mg/d. His symptoms improve, but he experiences dose-limiting sialorrhea. Risperidone, 1 mg/d, is added to clozapine, which helps his psychosis and improves his functional status. Additionally, Mr. C develops enough insight to recognize his delusions and use skills learned in psychotherapy to cope with them. Antipsychotic polypharmacy (APP), the concurrent use of [greater than or equal to] 2 antipsychotics, is a topic of debate among mental health care providers. Studies indicate the prevalence of APP can reach upwards of 40%, with 1 systematic review citing more recent median APP prevalence in North America as 17%, an increase from a median of 12.7% in the 1980s. (1) Other studies cite more recent figures as around 20%. (2-3) The literature lists several reasons for use of long-term APP, including: * incomplete cross-titration * accidental continuation of APP that was intended to be temporary * monotherapy failure * mitigation or enhancement of effects of other antipsychotics (Table 1). (1,4) Other factors include direct-to-consumer advertising, external pressures to decrease hospital stays, and low doctor-to-patient ratios. (5) Although it can take as long as 16 weeks to see clinically significant improvement with an antipsychotic, prescribers might expect results after 4 weeks of treatment. (6) Therefore, treatments could be labeled ineffective because trials did not last long enough, leading to premature use of polypharmacy. Combinations of a first- and second-generation antipsychotic (SGA) or 2 SGAs are most common. (2,7,8) Treatment guidelines (Table 2, page 52) (9-17) suggest APP could be considered after several failures of monotherapy, including clozapine monotherapy, although some guidelines do not address the issue or recommend against APP because of lack of efficacy and safety data. Additionally, APP poses safety concerns (Table 3, page 52). (18,22) Recommendations for APP with combinations that do not include clozapine generally are not provided, because high-level evidence to support this strategy is lacking. Data on safety and efficacy of APP are mixed, with much of the literature dominated by case reports and uncontrolled studies. (19) What to initiate Clozapine.'Higher-level evidence is available for clozapine APP. The combination of clozapine and risperidone is one of the most thoroughly studied and, therefore, is a reasonable first choice. Randomized controlled trials (RCTs) examining clozapine plus risperidone (23-29) have yielded mixed results and have not provided conclusive information regarding benefit for positive vs negative symptoms. (24-28) One RCT reported a significant change in Brief Psychiatric Rating Scale (BPRS) total and positive symptom scores. (27) Other RCTs have shown a non-significant trend toward greater change in total, positive, and negative symptom scores with the clozapine-risperidone combination compared with clozapine monotherapy. (25,28) In terms of cognition, this combination provided no additional benefit. (23) Response, defined as [greater than or equal to] 20% reduction in total BPRS or Positive and Negative Syndrome Scale (PANSS) scores, for clozapine plus risperidone range from 13% to 83%, compared with 8% to 29% for clozapine plus placebo. (24,25,27,29) Data from 1 study (27) suggest a number needed to treat of 4 to achieve at least a 20% improvement in BPRS scores with clozapine plus risperidone vs clozapine monotherapy. …

Rebecca L. Graham

Papers

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

PTSD Nightmares: Prazosin and Atypical Antipsychotics

When and Why to Initiate Antipsychotic Polypharmacy, and with Which Agents