Exploring the Efficacy of Ketamine as an Anesthetic and Antidepressant in Postpartum Depression: A Case Study Analysis.

Postpartum depression is a common mental health disorder that affects women within six months after giving birth. It is characterized by sadness, anxiety, and extreme fatigue, which can significantly impact a woman's daily functioning and ability to care for her newborn. While traditional treatments for postpartum depression include therapy and medication, recent studies have shown promising results using ketamine. We present a case of a woman with a history of depression who delivered four children by cesarean section with debilitating postpartum depression in two births and no symptoms of depression in the births where she received ketamine during delivery.

Nortriptyline-Induced Room Tilt Illusion.

Room tilt illusion (RTI) is a rare and transient perceptual disturbance in which an individual perceives their surroundings as having been rotated or tilted, usually at 90 or 180 degrees. Primarily linked with vestibular disorders and neurological lesions, this report details the only reported occurrence of the RTI phenomena in nortriptyline use for treatment-refractory depression. The patient developed RTI six days after starting the medication and the disturbance resolved after medication cessation. Although the mechanism behind such a phenomenon with medication use has not been elucidated, its etiology may rest on the effect of tricyclic antidepressants on the vestibulo-thalamo-cortical system and visual-vestibular integration. Clinicians should be aware of the potential for such a medication-induced perceptual disturbance, especially in the workup for more serious etiologies in elderly patients with co-morbidities.

Behind the Mask: Parkinson's Disease and Depression.

Parkinson's disease (PD) is a common, prevalent neurodegenerative disease. It is mainly characterized by motor symptoms such as rigidity, tremors, and bradykinesia, but it can also manifest with non-motor symptoms, of which depression is the most frequent. The latter can impair the quality of life, yet it gets overlooked and goes untreated because of the significant overlap in their clinical features, hence making the diagnosis difficult. Furthermore, there is limited data on the availability of appropriate criteria for making the diagnosis of depression in PD patients, as it can occur with varying expressions throughout the course of PD or it can also precede it. This review article has included a brief discussion on the diagnosis of depression in PD patients and their overlapped clinical manifestations. Understanding the mechanisms underlying the disease processes of PD and depression and the pathways interconnecting them gives better knowledge on devising treatment options for the patients. Only studies from Pubmed were included and all other databases were excluded. Studies from the last 50 years were included. Suitable references included in these studies were also extracted. Thus, depression in PD and PD in depression, along with their pharmacological and non-pharmacological treatment options, have been discussed.

Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review.

The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.

Imipramine Suppresses Tumor Growth and Induces Apoptosis in Oral Squamous Cell Carcinoma: Targeting Multiple Processes and Signaling Pathways.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) has limited treatment options. This study investigated imipramine, a tricyclic antidepressant, as a potential therapy for OSCC using a SAS-bearing xenograft animal model. MATERIALS AND METHODS: The SAS-bearing xenograft model evaluated imipramine's impact on tumor growth. The control group received no treatment, while the imipramine-treated group received regular doses. Tumor growth, confirmed by imaging, and histological analysis assessed size and weight. Imipramine's effects on apoptosis, epithelial-to-mesenchymal transition (EMT), and transcription factors (AKT, ERK, STAT3) were analyzed. RESULTS: Imipramine significantly suppressed tumor growth within 6 days of treatment, with sustained activity. Computer tomography (CT) scans and histology confirmed reduced size and weight by imipramine. Imipramine induced apoptosis via caspase-dependent/-independent pathways, inhibited EMT, and down-regulated phosphorylated AKT, ERK, and STAT3. CONCLUSION: Imipramine shows promise as an effective OSCC therapy, inhibiting tumor growth, inducing apoptosis, and inhibiting EMT. Its impact on transcription factors and modulation of the AKT/ERK/STAT3 pathway suggest a multifaceted approach.

Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants.

The novel mechanisms of action (MOA) derived from some recently introduced molecular targets have led to regulatory approvals for rapid acting antidepressants (RAADs) that can generate responses within hours or days, rather than weeks or months. These novel targets include the N-methyl-D-glutamate receptor antagonist ketamine, along with its enantiomers and various derivatives, and the allosteric modulators of gamma-aminobutyric acid (GABA) receptors. There has also been a strong resurgence in interest in psychedelic compounds that impact a range of receptor sites including D1, 5-HT7, KOR, 5-HT5A, Sigma-1, NMDA, and BDNF. The RAADs developed from these novel targets have enabled successful treatment for difficult to treat depressed individuals and has generated a new wave of innovation in research and treatment. Despite the advances in the neurobiology and clinical treatment of mood disorders, we are still using rating instruments that were created decades ago for drugs from a different era (e.g., The Hamilton and Montgomery-Åsberg depression rating scales, HDRS, and MADRS) continue to be used. These rating instruments were designed to assess mood symptoms over a 7-day time frame. Consequently, the use of these rating instruments often requires modifications to address items that cannot be assessed in short time frames, such as the sleep and appetite items. This review describes the adaptative approaches that have been made with the existing scales to meet this need and examines additional domains such as daily activities, side effects, suicidal ideation and behavior, and role functioning. Recommendations for future studies are described, including the challenges related to implementation of these adapted measures and approaches to mitigation.

A Complete Sojourn of Gene Therapy along with its Targeting Approaches for the Treatment of the Major Depressive Disorder.

Approximately 2% to 3% of men and 6% to 7% of women suffer from severe depressive disorders. The existing drugs only partially relieve symptoms for roughly 40% of these patients. The majority of antidepressant drugs are based on theories that are now 50 to 60 years old, and the sector is in critical need of new drug development targets. In the recent decade, numerous genes have been connected to depression in animal models, and serious depression does run in families in humans, indicating both a genetic and environmental component. Depression has been linked to the malfunctioning of serotonin signaling genes, including p11, SERT, etc, according to earlier research. Gene therapy for depression has been found in some instances to be relatively safe, despite the fact that it may seem riskier and more invasive than medication. Hence, there is a growing field regarding the safest delivery mechanisms of these genes that treat major depressive disorders permanently. Hence, the present review summarized the delivery mechanisms of various genes responsible for depressive disorders along with their molecular mechanisms and delivery at the cellular level.

Factors Associated With Non-adherence to Anti-depressant Medication in Adults: A Systematic Review and Meta-Analysis.

The present meta-analysis has been conducted to review currently available literature to examine the factors associated with adherence to anti-depressant medications in adults. This meta-analysis and systematic review followed the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. According to this analysis, the three most important electronic resources for research were CINAHL, EMBASE, and Medline. Google Scholar was used to supplementing the articles already available for review. Keywords used to find relevant articles included "predictors," "non-adherence," "anti-depressants," and "adults." Medical subject headings (MeSH) terms and Boolean operators ("AND" and "OR") were used in the search strategy to refine the search further. Studies included in this meta-analysis had information on factors associated with non-adherence to anti-depressant medication. The study evaluated samples of adult participants over 18 years with a diagnosis of depression and who had been prescribed anti-depressants. In conclusion, this meta-analysis examined the relationship between demographic factors and non-adherence to anti-depressant medications. The findings revealed that gender, educational status, income level, marital status, and area of residence did not significantly predict non-adherence to anti-depressants. However, older age and polypharmacy were significant predictors of adherence to anti-depressants. The study also found that individuals living in urban areas were more likely to adhere to anti-depressants, but the difference was not statistically significant.

Machine learning prediction will be part of future treatment of depression.

Machine learning (ML) is changing the way that medicine is practiced. While already clinically utilised in diagnostic radiology and outcome prediction in intensive care unit, ML approaches in psychiatry remain nascent. Implementing ML algorithms in psychiatry, particularly in the treatment of depression, is significantly more challenging than other areas of medicine in part because of the less demarcated disease nosology and greater variability in practice. Given the current exiguous capacity of clinicians to predict patient and treatment outcomes in depression, there is a significantly greater need for better predictive capability. Early studies have shown promising results. ML predictions were significantly better than chance within the sequenced treatment alternatives to relieve depression (STAR*D) trial (accuracy 64.6%, p < 0.0001) and combining medications to enhance depression outcomes (COMED) randomised Controlled Trial (RCT) (accuracy 59.6%, p = 0.043), with similar results found in larger scale, retrospective studies. The greater flexibility and dimensionality of ML approaches has been demonstrated in studies incorporating diverse input variables including electroencephalography scans, achieving 88% accuracy for treatment response, and cognitive test scores, achieving up to 72% accuracy for treatment response. The predicting response to depression treatment (PReDicT) trial tested ML informed prescribing of antidepressants against standard therapy and found there was both better outcomes for anxiety and functional endpoints despite the algorithm only having a balanced accuracy of 57.5%. Impeding the progress of ML algorithms in psychiatry are pragmatic hurdles, including accuracy, expense, acceptability and comprehensibility, and ethical hurdles, including medicolegal liability, clinical autonomy and data privacy. Notwithstanding impediments, it is clear that ML prediction algorithms will be part of depression treatment in the future and clinicians should be prepared for their arrival.

Measuring anxiety disorder in bipolar disorder using EVestG: broad impact of medication groups.

Objectives: Anxiety disorder is present in approximately half of all bipolar disorder (BD) patients. There are neurologic bases for the comorbidity of balance (vestibular) disorders and anxiety. Our objective is to use electrovestibulography (EVestG), which is predominantly a measure of vestibular neural activity to not only quantitatively detect and measure comorbid anxiety disorder but also to quantitatively measure the impacts of anti-depressant, anti-psychotic, and mood stabilizer medication groups on anxiety measures in BD patients. Methods: In a population of 50 (24 with anxiety disorder) depressive phase BD patients, EVestG signals were measured. Participants were labeled depression-wise as anxious or non-anxious using standard questionnaires. Analyses were conducted on the whole dataset as well as on matched (age/gender/MADRS) and "modeled medication-free" subsets. Modulations of the low-frequency EVestG firing pattern data were measured. Findings: For BD, the main anxious minus non-anxious difference was the presence of an increase in spectral power proximal to 8-9 Hz, which was best attenuated by mood stabilizers. Novelty: This is the first study to use an oto-acoustic physiological measure to quantify anxiety disorder in BD wherein it appears to manifest as a peak proximal to 8-9 Hz which we hypothesize as likely linked to hippocampal theta.

Pharmacogenetic Expression of CYP2C19 in a Pediatric Population.

Genetic variability in CYP2C19 may be associated with both lack of efficacy and toxicity of drugs due to its different metabolic status based on the presence of particular alleles. This literature review summarizes current knowledge relative to the association or treatment adaptation based on CYP2C19 genetics in a pediatric population receiving drugs metabolized by CYP2C19, such as voriconazole, antidepressants, clopidogrel and proton pump inhibitors. Additionally, we also presented one of the approaches that we developed for detection of variant alleles in the CYP2C19 gene. A total of 25 articles on PubMed were retained for the study. All studies included pediatric patients (age up to 21 years) having benefited from an assessment of CYP2C19. CYP2C19 poor and intermediate metabolizers exhibit a higher trough plasma concentration of voriconazole, and PPIs compared to the rapid and ultra-rapid metabolizers. The pharmacogenetic data relative to CYP2C19 and clopidogrel in the pediatric population are not yet available. CYP2C19 poor metabolizers have a higher trough plasma concentration of antidepressants compared to the rapid and the ultra-rapid metabolizers. Modification of allele-specific PCR through the introduction of artificial mismatch is presented. CYP2C19 genotyping remains a powerful tool needed to optimize the treatment of children receiving voriconazole, PPIs, and anti-depressants.

The evaluation of the 3-30-300 green space rule and mental health.

BACKGROUND AND AIMS: Urban green space has many health benefits, but it is still unclear how much actually is needed for better health. Recently a new 3-30-300 rule of thumb for urban forestry and urban greening has been proposed, but this rule has not been evaluated for benefits on health. The rule requires that every citizen should be able to see at least three trees from their home, have 30 percent tree canopy cover in their neighbourhood and not live more than 300 m away from the nearest park or green space. The aim of this study was to evaluate the relationship between the 3-30-300 green space rule and its components in relation to mental health. METHODS: We conducted a cross-sectional study based on a population-based sample of 3145 individuals aged 15-97 years from in Barcelona, Spain who participated in the Barcelona Health Survey (2016-2017). We created 3-30-300 green space indicators using questionnaire data, GIS, remote sensing and land cover maps. Mental health status was assessed with the 12-item General Health Questionnaire (GHQ-12) and also the use of tranquilizer/sedatives or antidepressants and psychiatrist or psychologist visits. Analyses were conducted using mixed effects logistic regression models with districts as the random effect, adjusted for relevant covariates. RESULTS: We found that people in Barcelona had relatively little exposure to green space, whether through window view, living in an area with sufficient greenness, or access to a major green space, and only 4.7% met a surrogate 3-30-300 green space rule. Residential surrounding greenness, but not tree window view or access to major green space, was significantly associated with better mental health, less medication use, and fewer psychologist or psychiatrist visits. Meeting the full surrogate 3-30-300 green space rule was associated with better mental health, less medication use, and fewer psychologist or psychiatrist visits, but only for the latter combined the association was statistically significant (Odds ratio = 0.31, 95% CI: 0.11, 0.91). CONCLUSION: Few people achieved the 3-30-300 green space in Barcelona and we used a surrogate measure. We observed health benefits when the full surrogate rule was met.

Cost-effectiveness of esketamine nasal spray compared to intravenous ketamine for patients with treatment-resistant depression in the US utilizing clinical trial efficacy and real-world effectiveness estimates.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of esketamine nasal spray relative to intravenous ketamine for patients with treatment-resistant depression (TRD) in the US. METHODS: We used a Markov model with a 1-month cycle length, and we estimated quality-adjusted life years (QALYs), costs (2020 USD), and incremental cost-effectiveness ratios (ICER) of esketamine relative to ketamine over a 3-year time horizon, from both the healthcare sector and patient perspectives. We ran the model using efficacy estimates from both clinical trial and real-world effectiveness (RWE) data. One-way and probabilistic sensitivity analyses (PSAs) were performed to evaluate the robustness of findings. RESULTS: Over a 3-year time horizon, the use of esketamine yielded 1.98 QALYs (RWE/clinical trial efficacy), and the use of ketamine yielded 2.03 QALYs (clinical trial efficacy) or 1.99 QALYs (RWE). Esketamine was dominated by ketamine using the healthcare perspective. ICERs were above $150,000/QALY threshold with the patient perspective. Under the healthcare perspective, PSA showed there are no scenarios where esketamine was cost-effective compared to ketamine. With the patient's perspective, the probability that esketamine was cost-effective compared to ketamine was 0.0055 (clinical trial efficacy) and 0.35 (RWE). LIMITATIONS: The data utilized for efficacy have limitations. The time horizon may fail to capture longer-term costs and benefits. CONCLUSIONS: In this decision analytic model evaluating esketamine versus ketamine for TRD, we found esketamine unlikely to be cost-effective under a healthcare sector perspective. Under a patient perspective, esketamine had similar effectiveness and was less costly than ketamine due to insurance coverage.

Anti-Depressant Properties of Crocin Molecules in Saffron.

Saffron is a valued herb, obtained from the stigmas of the C. sativus Linn (Iridaceae), with therapeutic effects. It has been described in pharmacopoeias to be variously acting, including as an anti-depressant, anti-carcinogen, and stimulant agent. The therapeutic effects of saffron are harbored in its bioactive molecules, notably crocins, the subject of this paper. Crocins have been demonstrated to act as a monoamine oxidase type A and B inhibitor. Furthermore, saffron petal extracts have experimentally been shown to impact contractile response in electrical field stimulation. Other research suggests that saffron also inhibits the reuptake of monoamines, exhibits N-methyl-d-aspartate antagonism, and improves brain-derived neurotrophic factor signaling. A host of experimental studies found saffron/crocin to be similarly effective as fluoxetine and imipramine in the treatment of depression disorders. Saffron and crocins propose a natural solution to combat depressive disorders. However, some hurdles, such as stability and delivery, need to be overcome.

Anti-inflammatory properties of commonly used psychiatric drugs.

Mental health and neurodevelopmental disorders are extremely common across the lifespan and are characterized by a complicated range of symptoms that affect wellbeing. There are relatively few drugs available that target disease mechanisms for any of these disorders. Instead, therapeutics are focused on symptoms and syndromes, largely driven by neurotransmitter hypotheses, such as serotonin or dopamine hypotheses of depression. Emerging evidence suggests that maternal inflammation during pregnancy plays a key role in neurodevelopmental disorders, and inflammation can influence mental health expression across the lifespan. It is now recognized that commonly used psychiatric drugs (anti-depressants, anti-psychotics, and mood stabilizers) have anti-inflammatory properties. In this review, we bring together the human evidence regarding the anti-inflammatory mechanisms for these main classes of psychiatric drugs across a broad range of mental health disorders. All three classes of drugs showed evidence of decreasing levels of pro-inflammatory cytokines, particularly IL-6 and TNF-α, while increasing the levels of the anti-inflammatory cytokine, IL-10. Some studies also showed evidence of reduced inflammatory signaling via nuclear factor- (NF-)κB and signal transducer and activator of transcription (STAT) pathways. As researchers, clinicians, and patients become increasingly aware of the role of inflammation in brain health, it is reassuring that these psychiatric drugs may also abrogate this inflammation, in addition to their effects on neurotransmission. Further studies are required to determine whether inflammation is a driver of disease pathogenesis, and therefore should be a therapeutic target in future clinical trials.

Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder.

Patients with epilepsy can experience different neuropsychiatric symptoms related (peri-ictal) or not (interictal) with seizures. Peri-ictal symptoms can precede (pre-ictal) or follow (post-ictal) the seizure, or even be the expression of the seizure activity (ictal). Neuropsychiatric symptoms, such as irritability and apathy, are among the most frequent pre-ictal manifestations. Ictal fear is reported by around 10% of patients with focal seizures, and sometimes can be difficult to differentiate from panic attacks. Post-ictal anxiety, mood and psychotic symptoms are also frequently reported by patients. Peri-ictal phenomena can occur as isolated symptom or as a cluster of symptoms, sometimes resembling a full-blown psychiatric syndrome. Actually, peri-ictal and interictal neuropsychiatric manifestations seem to be closely associated.

Adverse Drug Reactions Associated With Drugs Prescribed in Psychiatry: A Retrospective Descriptive Analysis in a Tertiary Care Hospital.

Background Psychiatric disorders are chronic in nature which often require long and continuous medications. These medications are known to cause adverse effects on their use. Their monitoring and prevention are crucial for the practicing family and community physicians. Method This is a cross-sectional retrospective study conducted to analyze all the spontaneous adverse drug reactions (ADRs) reported from the psychiatry department to the ADR Monitoring Center, Department of Pharmacology, AIIMS Jodhpur during the time period from 2014 to 2020. Results A total of 334 ADRs were reported. The majority of the ADRs were reported from antipsychotics (60.6%) followed by antidepressants (25.5%) and antiepileptic drugs (5.8%). On further subgroup analysis of the drug classes among antipsychotics, Clozapine (15.8%) was the leading offending agent. Similarly, among Antidepressants, Escitalopram (6.1%) was causing the most side effects. The most common ADR reported was sedation (7.26%) followed by salivary hypersecretion (6.7%), akathisia (5.52%), and weight gain (5.52%). Conclusion Knowledge of common ADRs help in better management of the diseases and psychotropics as a class has various frequents ADRs. Early detection and suitable intervention can help the community physicians in the proper care of the patients and rational use of drugs.

Emerging Role of Flavonoids as the Treatment of Depression.

Depression is one of the most frequently observed psychological disorders, affecting thoughts, feelings, behavior and a sense of well-being in person. As per the WHO, it is projected to be the primitive cause of various other diseases by 2030. Clinically, depression is treated by various types of synthetic medicines that have several limitations such as side-effects, slow-onset action, poor remission and response rates due to complicated pathophysiology involved with depression. Further, clinically, patients cannot be given the treatment unless it affects adversely the job or family. In addition, synthetic drugs are usually single targeted drugs. Unlike synthetic medicaments, there are many plants that have flavonoids and producing action on multiple molecular targets and exhibit anti-depressant action by affecting multiple neuronal transmissions or pathways such as noradrenergic, serotonergic, GABAnergic and dopaminergic; inhibition of monoamine oxidase and tropomyosin receptor kinase B; simultaneous increase in nerve growth and brain-derived neurotrophic factors. Such herbal drugs with flavonoids are likely to be useful in patients with sub-clinical depression. This review is an attempt to analyze pre-clinical studies, structural activity relationship and characteristics of reported isolated flavonoids, which may be considered for clinical trials for the development of therapeutically useful antidepressant.

The Effects of Depression and Anti-Depressants on Quality of Life After Breast Reconstruction: A Post-Hoc Analysis.

Background A personal history of depression prior to breast cancer diagnosis and its effect on post-diagnosis quality of life (QOL) in women undergoing breast reconstruction is relatively unknown. We performed the current study to determine if depression alters QOL for patients who undergo breast reconstruction by assessing the pre-to-post-operative change in patient-reported BREAST-Q scores. Methodology We conducted a single-center, post-hoc analysis of 300 patients with completed BREAST-Q data who underwent breast reconstruction from November 2013 to November 2016 following a diagnosis of breast cancer. Patients completed the BREAST-Q at four time points: pre-operatively, six weeks following tissue expander (TE) insertion for patients undergoing staged reconstruction, and six and 12 months following the final reconstruction. Medical records were reviewed to identify patients who had a pre-cancer diagnosis of clinical depression and/or anti-depressant medication use. BREAST-Q scores were compared between groups and within groups. Groups compared were the depression (n = 50) and no depression (n = 250) patients, along with anti-depressant (n = 36) and no anti-depressant (n = 14) use in the depression group. Results Within-group Sexual Well-being scores at the six-week post-TE follow-up for patients in the depression group (median = 37, interquartile range [IQR] = 25-47) were significantly lower (p < 0.01) than the scores for patients in the no depression group (median = 47, IQR = 39-60). There were no statistically significant differences in BREAST-Q scores in other domains. When compared to patients diagnosed with depression who were not taking anti-depressants, anti-depressant medication use did not result in statistically significant higher BREAST-Q scores, although Satisfaction With Breasts six months post-operatively, Psychosocial Well-being at six weeks post-TE, Sexual Well-being at six weeks post-TE and six months post-operatively were clinically higher in patients taking anti-depressants for depression. Conclusions Patients with a diagnosis of depression prior to breast cancer had lower BREAST-Q Sexual Well-being scores in the six-week TE group with or without anti-depressant medication. Patients with a pre-cancer diagnosis of depression considering TEs may benefit from additional counseling prior to breast reconstruction or electing a different method of breast reconstruction. Anti-depressant medications may provide clinically higher BREAST-Q scores in patients with a pre-cancer diagnosis of depression. Adding an anti-depressant medication to a patient's treatment plan may provide additional benefits. Larger samples are required to properly determine the impact of anti-depressant medications on BREAST-Q scores in patients with a pre-cancer diagnosis of depression.

Are Psychotropic Medications Effective in Chronic Pain Management in Children and Adolescents? A Meta-Analysis of Randomized Control Trials.

OBJECTIVE: Data defining and subsequently guiding the use of psychotropic medications in children and adolescents is sparse. We conducted a meta-analysis of randomized control trials to examine the effectiveness of psychotropic medications in children and adolescents with chronic pain. METHODS: We conducted a comprehensive literature search from published studies, and annual scientific sessions of psychiatry conferences. We identified double-blind, randomized control trials (RCTs) in which psychotropic medications were compared to placebo. Data was collected for the total number of patients, baseline characteristics, and changes in pain score. Meta-analysis was performed using a random effect model evaluating average change in pain score and the number of patients with a reduction in pain score for both groups. Pooled data are expressed as standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found 5 studies that included amitriptyline (n=2), citalopram (n=1), buspirone (n=1) and duloxetine (n=1). In the pooled analysis for the difference in the average change in pain score, 4 RCTs with 395 patients were included. After 12-13 weeks of therapy, reductions in pain score were significantly greater in the psychotropic drug group as compared to placebo (SMD: -0.77, 95% CI -1.54, 0.0001, p= 0.05). For the analysis on the number of patients with a reduction in pain, data were available for 445 patients (224-medication group, 221-placebo group). More patients in the psychotropic drug group experienced a meaningful reduction in pain score at 12-13 weeks of therapy compared to placebo (OR 1.66, 95% CI 1.08-2.54, p= 0.02). CONCLUSION: The results of this meta-analysis demonstrate significant analgesic efficacy of psychotropic medications in the management of children with chronic pain. This review is limited by the small number of studies included for analysis. There is a pressing need for more robust clinical trials to further investigate these promising findings.