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.

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

These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the recommendations will help to inform clinical decision making for practitioners, and perhaps also serve as a source of information for patients and carers. They are accompanied by a more detailed qualitative review of the available evidence. The strength of supporting evidence for each recommendation is rated.

https://journals.sagepub.com/doi/pdf/10.1177/0269881119889296

Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology:

Newer generation antidepressant drugs (ADs) are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents. In this critical review, we evaluated the literature on adverse events, tolerability and safety of selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later. They encompass gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia), hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular disturbances (heart rate, QT interval prolongation, hypertension, orthostatic hypotension), genitourinary symptoms (urinary retention, incontinence), sexual dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central nervous system disturbances (lowering of seizure threshold, extrapyramidal side effects, cognitive disturbances), sweating, sleep disturbances, affective disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations (glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas of concern involve suicidality, safety in overdose, discontinuation syndromes, risks during pregnancy and breast feeding, as well as risk of malignancies. Thus, the rational selection of ADs should consider the potential benefits and risks, likelihood of responsiveness to the treatment option and vulnerability to adverse events. The findings of this review should alert the physician to carefully review the appropriateness of AD prescription on an individual basis and to consider alternative treatments if available.

/pdf/the-safety-tolerability-and-risks-associated-with-the-use-of-1iofn1zl6x.pdf

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature.

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(09)00201-6.pdf

New perspectives on the neurodevelopmental effects of SSRIs

Importance Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population. Context There are conflicting data regarding potential risks of prenatal antidepressant treatment. Objective To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. Data Sources MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. Study Selection English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this meta-analysis. Data Extraction Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers. Results There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks], −0.45; 95% CI, −0.64 to −0.25; P  Conclusions and Relevance Although statistically significant associations between antidepressant exposure and pregnancy and delivery outcomes were identified, group differences were small and scores in the exposed group were typically within the normal ranges, indicating the importance of considering clinical significance. Treatment decisions must weigh the effect of untreated maternal depression against the potential adverse effects of antidepressant exposure.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/1656691/yma120004_436_443.pdf

Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis.

Objectives: To identify symptoms in neonates exposed to antidepressants in late pregnancy and to propose a categorization of these symptoms to help clinical assessment of antidepressant effects in exposed neonates. Methods: Data were extracted retrospectively from maternal and neonatal hospital charts. A total of 73 neonates exposed to antidepressant and 73 nonexposed neonates were included. Neonatal symptoms reported in the literature to be related to antidepressant exposure were collected. Multiple logistic regression analysis was used to estimate the association of neonatal symptoms and antidepressant exposure. Factorial analysis was used to regroup the neonatal symptoms. Results: Increased risk of alertness alteration (odds ratio [OR], 37;95% confidence interval [CI], 8-174), altered muscular tone (OR,20; 95% CI, 5-71), feeding and GI problems (OR, 3.8; 95% CI, 1.7-8.1), tachypnea (OR, 2.5; 95% CI, 1.1-5.3), and neurological problems (8/73 vs 0/73; P = 0.006) were found. Three statistically significant clusters of symptoms associated with antidepressant exposures emerged from the factorial analysis. Two of these clusters were similar to those described in adults for serotonergic toxicity and antidepressant discontinuation syndrome while the other was closely related to neonatal immaturity. Conclusions: Symptoms expressed in neonates exposed to antidepressants in late pregnancy could be gathered in three clusters. This grouping could be useful to develop a new tool helping in the assessment and care of the exposed newborns.

A new look at the neonate's clinical presentation after in utero exposure to antidepressants in late pregnancy.

The nature of neonatal adverse effects in the offspring after maternal use of venlafaxine at term is not fully understood. We correlated neonatal clinical signs over time with serum concentrations of venlafaxine and its active metabolite in the neonatal period. Women exposed to venlafaxine near term, and their neonates, were studied. Adverse neonatal signs and serum concentrations of venlafaxine and its active metabolite were assessed. Seven mother-child pairs were studied. Median maternal venlafaxine dose was 75 mg/d (37.5-300 mg/d). Five neonates presented with multiple clinical signs during their hospital stay, all including tachypnea and respiratory distress. Respiratory distress was present within the first hours after birth, with other symptoms appearing subsequently when the drug concentration declined. The elimination half-life, calculated for 3 neonates, ranged between 12 and 15 hours for venlafaxine and between 10 and 37 hours for O-desmethylvenlafaxine. Neonatal clinical signs emerged as drug concentrations declined, corroborating discontinuation as an etiology. Respiratory symptoms tended to occur earlier and, in one case, independently from the typical signs of abrupt cessation of venlafaxine. This suggests that it may be part of the wide range of respiratory problems reported in antidepressant-exposed neonates, including persistent pulmonary hypertension of the newborn reported with selective serotonin reuptake inhibitor. Neonatal clinical signs emerged with decreasing concentrations of venlafaxine, supporting that abrupt cessation of venlafaxine leads to discontinuation syndrome. Respiratory problems occurred earlier than typical discontinuation clinical signs. Larger studies are needed to confirm these findings.

Maternal use of venlafaxine near term: correlation between neonatal effects and plasma concentrations.

Neonates exposed at term to selective serotonine (SSRI) or serotonine-norepinephrine reuptake inhibitors (SNRI) medications may encounter symptoms such as irritability, rigidity, tremor and respiratory distress. Most available data suggest that these self limited symptoms are due to discontinuation of the drug, although there are documented cases of symptoms associated with high serum concentrations in the neonate that subsided when levels fall. Preliminary evidence suggests that the very early respiratory symptoms may not be part of discontinuation but rather part of a reversible form of persistent pulmonary hypertension of the newborn (PPHN).

Adverse effects in neonates exposed to SSRIs and SNRI in late gestation--Motherisk Update 2008.

OBJECTIVE To assess whether prescribing physicians advised female patients taking isotretinoin according to pregnancy prevention recommendations, whether women understood those recommendations, and whether women complied with recommendations to prevent pregnancy. DESIGN Cross-sectional study designed to collect patients9 self-reported information. Women were interviewed by telephone with a standardized questionnaire. SETTING Quebec. PARTICIPANTS Participants were recruited through pharmacies, medical clinics, and newspapers in Quebec. All subjects (45 women 14 years and older) were treated with isotretinoin at the time of the interview or in the preceding 6 months. MAIN OUTCOME MEASURES Women9s self-report of their physician9s behaviour regarding prevention of pregnancy, women9s comprehension of the information, and their level of compliance with recommendations. RESULTS Prescribing physicians discussed the risks of teratogenesis with 93% of the women but gave written information to only 36% of them. Seventy-eight percent of the women admitted not using 2 contraceptive methods all the time during the treatment, and 3 women reported having had sexual intercourse without any contraception. Physicians prescribed a pregnancy test before treatment for 44% of the women. Only 18% of the women waited for their next menstrual period to begin isotretinoin treatment, and this advice was given by 20% of physicians. A statistically significant relationship between counseling and recommendations given by physicians and women9s use of double contraception was highlighted. CONCLUSION Female patients reported physicians did not always advise them according to recommendations concerning pregnancy prevention. Women understood the information received but did not fully comply. The extent of pregnancy prevention measures taken by physicians was linked to women9s compliance. Further study exploring underlying reasons for women9s noncompliance could provide information on changing such behaviour.

https://www.cfp.ca/content/cfp/52/3/338.full.pdf

Nina Boucher

Papers

A new look at the neonate's clinical presentation after in utero exposure to antidepressants in late pregnancy.

Maternal use of venlafaxine near term: correlation between neonatal effects and plasma concentrations.

Adverse effects in neonates exposed to SSRIs and SNRI in late gestation--Motherisk Update 2008.

Pregnancy prevention among women taking isotretinoin: failure to comply with the recommendations.

Neonatal Adverse Reactions After In Utero Exposure to Selective Serotonin Reuptake Inhibitors: Still Controversial