-
CNS Drugs Apr 2020Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.
METHODS
We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.
RESULTS
Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.
CONCLUSIONS
No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Central Nervous System Stimulants; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 32185696
DOI: 10.1007/s40263-020-00711-x -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
Asian Journal of Psychiatry Jan 2023To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for... (Meta-Analysis)
Meta-Analysis
Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.
OBJECTIVE
To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).
METHODS
Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.
RESULTS
We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).
CONCLUSION
Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).
Topics: Humans; Clozapine; Network Meta-Analysis; Entropy; Memantine; Mirtazapine; Antipsychotic Agents; Schizophrenia
PubMed: 36470132
DOI: 10.1016/j.ajp.2022.103375 -
Progress in Neuro-psychopharmacology &... Aug 2021Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and...
Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and family members. Despite its high prevalence, reaching 1/54 children and 1/45 adults in the United States, no pharmacological treatment is still directed to core symptoms of ASD, encompassing social and communication deficits, repetitive behaviors, restricted interests, and abnormal sensory processing. The purpose of this review is to provide an overview of the state-of-the-art of psychopharmacological therapy available today for ASD in children and adolescents, in order to foster best practices and to organize new strategies for future research. To date, atypical antipsychotics such as risperidone and aripiprazole represent the first line of intervention for hyperactivity, impulsivity, agitation, temper outbursts or aggression towards self or others. Tricyclic antidepressants are less prescribed because of uncertain efficacy and important side effects. SSRIs, especially fluoxetine and sertraline, may be effective in treating repetitive behaviors (anxiety and obsessive-compulsive symptoms) and irritability/agitation, while mirtazapine is more helpful with sleep problems. Low doses of buspirone have shown some efficacy on restrictive and repetitive behaviors in combination with behavioral interventions. Stimulants, and to a lesser extent atomoxetine, are effective in reducing hyperactivity, inattention and impulsivity also in comorbid ASD-ADHD, although with somewhat lower efficacy and greater incidence of side effects compared to idiopathic ADHD. Clonidine and guanfacine display some efficacy on hyperactivity and stereotypic behaviors. For several other drugs, case reports and open-label studies suggest possible efficacy, but no randomized controlled trial has yet been performed. Research in the pediatric psychopharmacology of ASD is still faced with at least two major hurdles: (a) Great interindividual variability in clinical response and side effect sensitivity is observed in the ASD population. This low level of predictability would benefit from symptom-specific treatment algorithms and from biomarkers to support drug choice; (b) To this date, no psychoactive drug appears to directly ameliorate core autism symptoms, although some indirect improvement has been reported with several drugs, once the comorbid target symptom is abated.
Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Humans; Psychopharmacology; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors
PubMed: 33857522
DOI: 10.1016/j.pnpbp.2021.110326 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Drug and Alcohol Dependence Mar 2022Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and methamphetamine use disorder (AMD). We evaluate the efficacy of mirtazapine in the treatment of AMD, given emerging evidence that it may alleviate methamphetamine and amphetamine (MA/A) cravings and withdrawals.
METHODS
We searched five databases from inception until January 28, 2021 for studies with a comparator group evaluating mirtazapine for treatment of AMD. We collected data on reduction in MA/A use, treatment retention, sexual behaviors, depression symptoms, cravings and adverse events. We assessed certainty of evidence using GRADE. Where appropriate, we conducted fixed-effect meta-analyses weighted by inverse variance and calculated the absolute risk reduction.
RESULTS
Among the 206 studies screened, we included two parallel-arm placebo-controlled RCTs conducted among cis-gender men and transgender women (n = 180). We found that mirtazapine use likely results in a small reduction of methamphetamine use compared to placebo after 12-weeks (relative risk [RR]=0.81, 95% confidence interval [CI]: 0.63, 1.03; n = 133; moderate certainty evidence due to imprecision). We also found that the use of mirtazapine probably does not improve retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence) or depression symptom severity (mean difference [MD]=0.45, 95% CI: -2.88, 3.78; n = 53; moderate certainty evidence). There were no serious adverse events.
CONCLUSIONS AND RELEVANCE
Mirtazapine probably results in a small reduction in continued methamphetamine use among cisgender men and transgender women with AMD, but probably does not improve patients' retention in treatment or depression symptom severity.
STUDY REGISTRATION
PROSPERO ID: CRD42021236806.
Topics: Central Nervous System Stimulants; Female; Humans; Male; Methamphetamine; Mirtazapine; Remission Induction; Substance-Related Disorders
PubMed: 35066460
DOI: 10.1016/j.drugalcdep.2022.109295 -
Journal of the American Geriatrics... Aug 2019To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess adverse effects of pharmacologic antidepressants for treatment of major depressive disorder (MDD) in adults 65 years of age or older.
DESIGN
Systematic review and meta-analysis.
SETTING
Specialist or generalist outpatient setting, rehabilitation facility, and nursing facilities.
PARTICIPANTS
Persons 65 years and older with MDD.
INTERVENTION
Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine compared with another antidepressant, placebo, or nonpharmacologic therapy.
MEASUREMENTS
Adverse events, arrhythmias, cognitive impairment, falls, fractures, hospitalization, mortality, QTc prolongation, serious adverse events, and withdrawals due to adverse events.
RESULTS
Nineteen randomized controlled trials and two observational studies were included. Most studies evaluated treatment of the acute phase (<12 wk) of MDD of moderate severity. SSRIs led to a statistically similar frequency of overall adverse events vs placebo (moderate strength of evidence [SOE]), but SNRIs caused more overall adverse events vs placebo (high SOE) during the acute treatment phase. Both SSRIs and SNRIs led to more study withdrawals due to adverse events vs placebo (SSRIs low SOE; SNRIs moderate SOE). Duloxetine led to a more falls vs placebo (moderate SOE) during 24 weeks of acute and continuation treatment of MDD.
CONCLUSION
In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs, but not SSRIs, was associated with a statistically greater number of overall adverse events vs placebo. SSRIs and SNRIs led to a greater number of study withdrawals due to adverse events vs placebo. Duloxetine increased the risk of falls that as an outcome was underreported in the literature. Few studies examined head-to-head comparisons, most trials were not powered to evaluate adverse events, and results of observational studies may be confounded. Comparative long-term studies reporting specific adverse events are needed to inform clinical decision making regarding choice of antidepressants in this population. J Am Geriatr Soc 67:1571-1581, 2019.
Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder, Major; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Observational Studies as Topic; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 31140587
DOI: 10.1111/jgs.15966 -
Journal of Perianesthesia Nursing :... Aug 2019Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients rank postoperative nausea and vomiting (PONV) as the most undesirable outcome of anesthesia. Mirtazapine is hypothesized to be effective in PONV prophylaxis via 5HT3 receptor antagonism.
DESIGN
Systematic review and meta-analysis.
METHODS
We identified seven randomized controlled trials by systematically searching electronic databases that compare the efficacy of mirtazapine versus placebo or ondansetron in reducing PONV.
FINDINGS
Mirtazapine reduced PONV overall versus placebo in three studies (risk ratio [RR] = 0.44; 95% confidence interval [CI] 0.32 to 0.62) both on conventional meta-analysis and trial sequential analysis. One study comparing mirtazapine with ondansetron found similar rates of PONV (RR = 0.96; 95% CI 0.48 to 1.94). Mirtazapine reduced preoperative anxiety versus placebo or ondansetron (standardized mean difference -1.4; 95% CI -2.56 to -0.23) but increased sedation (RR = 22.47; 95% CI 5.61 to 89.93). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was moderate to low.
CONCLUSIONS
This meta-analysis suggests that mirtazapine reduces PONV overall versus placebo. We found evidence of reduction in preoperative anxiety, although mirtazapine increased the risk of sedation.
Topics: Antiemetics; Humans; Mirtazapine; Postoperative Nausea and Vomiting
PubMed: 30879907
DOI: 10.1016/j.jopan.2018.11.006 -
Advances in Clinical and Experimental... Oct 2023Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
BACKGROUND
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain.
OBJECTIVES
To detect the negative modulators of the 5-HT2A receptor as a cure for ADP.
MATERIAL AND METHODS
The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events.
RESULTS
Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05).
CONCLUSION
Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.
Topics: Humans; Alzheimer Disease; Serotonin; Neurodegenerative Diseases; Activities of Daily Living; Drug Inverse Agonism; Receptor, Serotonin, 5-HT2A; Psychotic Disorders
PubMed: 37166012
DOI: 10.17219/acem/161159 -
Cureus Dec 2021Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone... (Review)
Review
Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone secretion is a condition characterized by excessive release of antidiuretic hormone from the pituitary gland or nonpituitary sources. One of the most common drugs associated with hyponatremia is selective serotonin reuptake inhibitors, especially in elderly patients. Therefore, distinct therapeutic alternatives are essential for patients having risk factors for hyponatremia or syndrome of inappropriate antidiuretic hormone secretion development. The present article aims to review the available literature evaluating mirtazapine-induced hyponatremia or syndrome of inappropriate antidiuretic hormone secretion in adult or elderly patients in order to determine the incidence of these adverse effects and analyze the existence of any correlation between the administered dose of mirtazapine and serum sodium levels. A systematic search was conducted, using key terms from the research topic, their synonyms, and Boolean/logic operators. From this evidence pool, inclusion and exclusion criteria were applied. We abstracted population characteristics and clinical endpoints. Relevant data from selected studies was abstracted and subject to statistical analysis. A total sample size of 30,851 patients treated with mirtazapine was included. Mirtazapine-induced hyponatremia incidence was 3.26% (95% CI 3.06-3.45%), with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) the most probable underlying cause. Among case series and case reports evaluated (n=7), hyponatremia and SIADH were more frequent in female patients (71.4%) and the most frequent clinical manifestations included confusion (57%), somnolence (42%), and altered speech (28%). Mean serum sodium levels were (117 mEq/L, ranging from 113-130 mEq/L). The average time lapse between mirtazapine administration and clinical findings was 34 days. The Spearman's rank correlation coefficient between mirtazapine dosage and serum sodium levels was -0.3181 with a p-value >0.05. In conclusion, mirtazapine presents a moderate risk of hyponatremia and should be considered as an alternative therapy in patients requiring antidepressants with risk factors for this preventable adverse effect.
PubMed: 35141079
DOI: 10.7759/cureus.20823