Bipolar disorders, including bipolar I disorder (BP-I) and bipolar II disorder (BP-II), are common, potentially disabling, and, in some cases, life-threatening conditions. Bipolar disorders are ...characterized by alternating episodes of mania or hypomania and depression, or mixtures of manic and depressive features. Bipolar disorders present many diagnostic and therapeutic challenges for busy clinicians. Adequate management of bipolar disorders requires pharmacotherapy and psychosocial interventions targeted to the specific phases of illness. Effective treatments are available for each illness phase, but mood episode relapses and incomplete responses to treatment are common, especially for the depressive phase. Mood symptoms, psychosocial functioning, and suicide risk must, therefore, be continually reevaluated, and, when necessary, the plan of care must be adjusted during long-term treatment. Many patients will require additional treatment of comorbid psychiatric and substance use disorders and management of a variety of commonly co-occurring chronic general medical conditions.
IMPORTANCE The increased prescribing of antipsychotics for children and youth has heightened concerns that this practice increases the risk of type 2 diabetes mellitus. OBJECTIVE To compare the risk ...of type 2 diabetes in children and youth 6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity score–matched controls who had recently initiated another psychotropic medication. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of the Tennessee Medicaid program with 28 858 recent initiators of antipsychotic drugs and 14 429 matched controls. The cohort excluded patients who previously received a diagnosis of diabetes, schizophrenia, or some other condition for which antipsychotics are the only generally recognized therapy. MAIN OUTCOMES AND MEASURES Newly diagnosed diabetes during follow-up, as identified from diagnoses and diabetes medication prescriptions. RESULTS Users of antipsychotics had a 3-fold increased risk for type 2 diabetes (HR = 3.03 95% CI = 1.73-5.32), which was apparent within the first year of follow-up (HR = 2.49 95% CI = 1.27-4.88). The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95% CI = 1.06-4.27), 3.42 (95% CI = 1.88-6.24), and 5.43 (95% CI = 2.34-12.61) for respective cumulative doses (gram equivalents of chlorpromazine) of more than 5 g, 5 to 99 g, and 100 g or more (P < .04). The risk remained elevated for up to 1 year following discontinuation of antipsychotic use (HR = 2.57 95% CI = 1.34-4.91). When the cohort was restricted to children 6 to 17 years of age, antipsychotic users had more than a 3-fold increased risk of type 2 diabetes (HR = 3.14 95% CI = 1.50-6.56), and the risk increased significantly with increasing cumulative dose (P < .03). The risk was increased for use restricted to atypical antipsychotics (HR = 2.89 95% CI = 1.64-5.10) or to risperidone (HR = 2.20 95% CI = 1.14-4.26). CONCLUSIONS AND RELEVANCE Children and youth prescribed antipsychotics had an increased risk of type 2 diabetes that increased with cumulative dose.
To examine whether a positive urine drug of abuse screen in youth who receive medical care is associated with subsequent risk of external mortality (eg, overdose, suicide, homicide, accident).
This ...was a population-based retrospective cohort study of all Olmsted County (Minnesota) residents who were 13-18 years of age at the time of urine drug screen (UDS) testing (January 1, 1999, to November 28, 2012). Cox regression models were used to examine the relationships between having a positive UDS and external mortality, adjusted for sex, race, age, alcohol exposure, psychiatric diagnoses as defined by the
(
/
), and medical setting of UDS testing. Separate analyses were done for (1) overall UDS results, (2) tetrahydrocannabinol (THC), and (3) cocaine.
Of the 2,772 teenagers included in this study (47.2% male), a total of 26 died of external causes during a median follow-up period of 11.8 years. Testing positive for any illicit substance was not associated with significantly increased risk of external mortality (hazard ratio HR = 1.9; 95% CI, 0.9-4.2). Testing positive for cocaine was associated with significantly increased risk of external mortality (HR = 7.0; 95% CI, 1.9-25.0). Testing positive for THC was associated with a marginally significantly increased risk of external mortality (HR = 2.1; 95% CI, 1.0-4.7); however, when cocaine was added as a covariate in the analysis, the relationship between THC-positive UDS and mortality was still elevated but was no longer statistically significant (HR = 1.8; 95% CI, 0.8-4.1).
History of cocaine-positive UDS may help identify a population of young people who are at high risk of premature death.
Severe persistent mental illness (SPMI) is associated with worse outcomes in cancer patients. Less is known about the relationship between SPMI and surgical outcomes after mastectomy for breast ...cancer.
We selected patients with breast cancer and SPMI from the National Inpatient Sample (2016–2018) and used propensity score matching. We then used multivariate analysis, Kruskal-Wallis tests, and conditional logistic regression to compare demographics and outcomes.
The study sample consisted of 670 patients: 536 without SPMI and 134 with SPMI. SPMI was associated with bilateral mastectomy (bilateral: 53% vs. unilateral: 42.7%, p = 0.033) and decreased frequency of breast reconstruction (p < 0.001). SPMI was associated with more extended hospitalization (4 days vs. 2 days, p < 0.001) and increased risk of developing post-procedural infection and sepsis (OR 2.909).
SPMI is associated with bilateral mastectomy, more extended hospitalization, and increased risk for post-procedural infection and sepsis – suggesting the need for increased use of standardized screening tools to identify SPMI in patients and inform perioperative management correctly.
•Severe persistent mental illness portends worse outcomes in breast cancer patients.•SPMI is associated with longer hospitalization after mastectomy.•SPMI is associated with more bilateral mastectomies and less breast reconstruction.•SPMI increases the risk of post-procedural infection and sepsis.•There is increased need for standardized screening to identify patients with SPMI.
Abstract Purpose To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009. Methods Retrospective cohort study of 277,555 ...pregnancies identified from birth and fetal death certificates, and linked to previously validated, computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios, and 95% confidence intervals (CI). Results During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI, 1.83–1.98), first trimester use increased 2.27-fold (95% CI, 2.14–2.41), and second or third trimester use increased 2.02-fold (95% CI, 1.93–2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in nonurban areas, enrolled in Medicaid owing to disability, and who had less than a high school education. Conclusions Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted to understand the implications of this increased use.
There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond ...poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side‐effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off‐label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence‐based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.
IMPORTANCE: Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks. OBJECTIVE: To examine ...associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions. DESIGN, SETTING, AND PARTICIPANTS: The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997–December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study’s data collection. EXPOSURES: Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants. MAIN OUTCOMES AND MEASURES: We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period. RESULTS: This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12–53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83). CONCLUSIONS AND RELEVANCE: We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.
Item 9 of the Patient Health Questionnaire (PHQ) evaluates passive thoughts of death or self-injury within the last two weeks, and is often used to screen depressed patients for suicide risk. We ...aimed to validate the PHQ-9 item 9 with a brief electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS).
We analyzed data from 841 patients enrolled in the National Network of Depression Centers Clinical Care Registry. We performed a validation analysis of PHQ-9 item 9 for suicide risk and ideation, using the eC-SSRS as a gold standard (defined as positive response to suicidal ideation with intent to act or recent suicidal behavior).
Of the 841 patients, 13.4% and 41.1% were assessed as being positive for suicide risk by the eC-SSRS and PHQ-9 item 9, respectively. For the overall cohort, sensitivity was 87.6% (95%CI 80.2–92.5%), specificity was 66.1% (95%CI 62.6–69.4%), PPV was 28.6% (95%CI 24.1–33.6%), and NPV was 97.2% (95%CI 95.3–98.3%) for the PHQ-9 suicide item. These performance measures varied within subgroups defined by demographic and clinical characteristics. In addition, the validity of PHQ-9 item 9 (cutoff score of 1) with eC-SSRS-defined suicide ideation showed overall poor results.
The gold standard used in our study was a surrogate measure of suicidality based on eC-SSRS scores.
The results of our study suggest that item 9 of the PHQ-9 is an insufficient assessment tool for suicide risk and suicide ideation, with limited utility in certain demographic and clinical subgroups that requires further investigation.
•The PHQ-9 item 9 is an insufficient assessment tool for suicide risk and ideation.•The PHQ-9 item 9 has limited utility in certain subgroups.•The PHQ-9 item 9 should be used with a validated suicide risk inventory.
Postpartum depression (PPD) is a common, potentially disabling, and, in some cases, life-threatening condition. Fortunately, PPD is also readily detectable in routine practice and is amenable to ...treatment by a wide variety of modalities that are effective for treating nonpuerperal major depression. Postpartum depression screening can improve case identification (an Edinburgh Postnatal Depression Scale score of ≥ 13 indicates a high risk of PPD) and, when associated with a diagnostic and follow-up program, leads to improved clinical outcomes. Symptom severity, patient preference, past response to treatment, availability of local mental health care resources, and patient decisions about breast-feeding will drive management decisions. In general, cognitive-behavioral therapy and interpersonal therapy are preferred psychotherapies for women with mild to moderate PPD, whereas antidepressants are appropriate in more severe cases. Many patients will require other types of assistance, such as parenting support, case management, or care coordination because many barriers to receiving adequate PPD treatment must still be overcome.
•This study was to assess whether three symptomatically defined phenotypes of MDD, (core depression, neurovegetative of melancholia and anxiety), could be differentiated based on acylcarnitine ...profiles at baseline, after eight weeks of citalopram/escitalopram treatment.•The current data demonstrated that these phenotypes have distinct patterns of acylcarnitine levels at baseline and after eight weeks of antidepressant treatment.•These findings may help to develop a metabolomic profile of MDD patients with the aim of improving subtype classification of the MDD syndrome.
Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+).
Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ®p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups.
Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+.
In depressed patients treated with SSRIs, β-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.
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