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BackgroundBetter indicators are needed for identifying children with early signs of developmental psychopathology.AimsTo identify measures of autonomic nervous system reactivity that discriminate children with internalising and externalising behavioural symptoms.MethodA cross-sectional study of 122 children aged 6--7 years examined sympathetic and parasympathetic reactivity to standardised field-laboratory stressors as predictors of parent- and teacher-reported mental health symptoms.ResultsMeasures of autonomic reactivity discriminated between children with internalising behaviour problems, externalising behaviour problems and neither. Internalisers showed high reactivity relative to low-symptom children, principally in the parasympathetic branch, while externalisers showed low reactivity, in both autonomic branches.ConclusionsSchool-age children with mental health symptoms showed a pattern of autonomic dimorphism in their reactivity to standardised challenges. This observation may be of use in early identification of children with presyndromal psychopathology.

Background: Instruments that are intended to measure change over time need to emphasize sensitivity to change as a central property. The aims of this report are to test whether the MOODS-SR, a measure of mood spectrum symptomatology, is sensitive to changes during acute and continuation treatment of depression and whether residual mood spectrum symptoms predict relapse in the subsequent 6 months.Methods: The study sample includes 316 patients with nonpsychotic depression participating in the protocol 'Depression: the search for treatment-relevant phenotypes'. Patients were initially randomized to selective serotonin reuptake inhibitors or interpersonal psychotherapy and then treated for 9 months using an algorithm-based protocol. Measures of mood symptomatology included the self-report version of the structured clinical interview for mood spectrum (MOODS-SR), the Quick Inventory for Depressive Symptomatology and the Hamilton Rating Scale for Depression.Results: Repeated-measures ANOVA indicates that during the acute phase MOODS scores decrease significantly from baseline to weeks 6 and 12. This decrease was significantly different (p < 0.001) between those who remitted and those who did not remit on the depressive, the rhythmicity component and the total score. Nonrelapsing subjects had stable scores across the continuation phase, while among relapsing subjects, a significant increase was found in the depressive component (p < 0.001), the rhythmicity component (p = 0.024) and the total score (p < 0.001), at 2 months, followed by a decrease from 2 to 6 months. Scores on the depressive component at the entry into continuation predicted relapse in the subsequent 6 months.Conclusions: Our findings suggest that the MOODS-SR is sensitive to change in depression status and may help the clinician to detect symptoms and signs not considered by established symptom severity scales. [ABSTRACT FROM AUTHOR]

Objective: The authors sought to determine whether a greater frequency of interpersonal psychotherapy (IPT) sessions during maintenance treatment has a greater prophylactic effect than a previously validated once-a-month treatment.Method: A total of 233 women 20-60 years of age with recurrent unipolar depression were treated in an outpatient research clinic. After participants had achieved remission with weekly IPT or, if required, with weekly IPT plus antidepressant pharmacotherapy, they were randomly assigned to weekly, twice-monthly, or monthly maintenance IPT monotherapy for 2 years or until a recurrence of their depression occurred.Results: Among participants who remitted with IPT alone and entered maintenance treatment (N=99), 19 (26%) of the 74 who remained in the study throughout the 2-year maintenance phase experienced a recurrence of depression. Among participants who required the addition of a selective serotonin reuptake inhibitor to achieve remission (N=90), 32 (36%) sustained that remission through continuation treatment and drug discontinuation and began maintenance treatment; of these, 13 (50%) of the 26 who remained in the study throughout the maintenance phase experienced a recurrence. Survival analysis of time to recurrence by randomized treatment frequency showed no effect on recurrence-free survival in either treatment subgroup.Conclusions: These results suggest that maintenance IPT, even at a frequency of only one visit per month, is a good method of prophylaxis for women who can achieve remission with IPT alone. In contrast, among those who require the addition of pharmacotherapy, IPT monotherapy represents a significantly less efficacious approach to maintenance treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHOD: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of /=11 (HRSD(17)>/=14) defined relapse. RESULTS: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether the disposition of the selective serotonin reuptake inhibitor, citalopram, could be robustly captured using 1 to 2 concentration samples per subject in 106 patients participating in 2 clinical trials. Nonlinear mixed-effects modeling was used to evaluate the pharmacokinetic parameters describing citalopram's disposition. Both a prior established 2-compartment model and a de novo 1-compartment pharmacokinetic model were used. Covariates assessed were concomitant medications, race, sex, age (22-93 years), and weight. Covariates affecting disposition were assessed separately and then combined in a stepwise manner. Pharmacokinetic characteristics of citalopram were well captured using this sparse sampling design. Two covariates (age and weight) had a significant effect on the clearance and volume of distribution in both the 1- and 2-compartment pharmacokinetic models. Clearance decreased 0.23 L/h for every year of age and increased 0.14 L/h per kilogram body weight. It was concluded that hyper-sparse sampling designs are adequate to support population pharmacokinetic analysis in clinically treated populations. This is particularly valuable for populations such as the elderly, who are not typically available for pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder. METHOD: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study. Patients were evaluated weekly with standard depression rating instruments and measures of psychosocial impairment. Hypotheses were tested by last-observation-carried-forward analysis of variance (ANOVA) and confirmed by mixed (random-effects) regression analysis. RESULTS: At baseline, minor depressive disorder patients were mildly to moderately depressed, with a corresponding degree of functional impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression severity scale. Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only. Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period. CONCLUSIONS: Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes. Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period. Improvement in psychosocial function with fluoxetine may take longer than 12 weeks. [ABSTRACT FROM AUTHOR]

BACKGROUND: Empirical data on the impact of personality pathology on acute treatment outcome for depression are mixed, in part because of challenges posed by assessing trait-like personality patterns while patients are in an active mood episode. To our knowledge, no previous study has examined the effect of personality pathology on maintenance treatment outcome. By maintenance treatment we refer to long-term treatment provided to prevent depression recurrence among remitted patients. METHOD: Structured Clinical Interviews for the DSM-III-R Personality Disorders (SCID-II) were obtained on a sample of 125 recurrently depressed women following sustained remission of the acute mood episode and prior to entering maintenance treatment. SCID-II interviews were then repeated following 1 and 2 years of maintenance interpersonal psychotherapy. RESULTS: At the pre-maintenance assessment, 21.6% of the sample met SCID-II personality disorder criteria. Co-morbid personality pathology was related to an earlier age of onset, more previous depressive episodes, and a greater need for adjunctive pharmacotherapy to achieve remission of the acute mood episode. Co-morbid personality pathology predicted both higher rates of depression recurrence and a shorter time to recurrence over the 2-year course of maintenance treatment. Notably, among those patients who remained depression-free, continuous levels of personality pathology steadily declined over the 2-year course of maintenance therapy. CONCLUSIONS: Results highlight the need for early and effective intervention of both episodic mood disorder and inter-episode interpersonal dysfunction inherent to the personality disorders. Future maintenance treatment trials are needed to clarify the relationship between episodic mood disorder and personality function over time. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study sought to evaluate the relationship of obesity to demographic and clinical characteristics and treatment outcome in a group of 175 patients with bipolar I disorder who were treated for an acute affective episode and followed through a period of maintenance treatment. METHOD: Data were from participants entering the Maintenance Therapies for Bipolar Disorder protocol between 1991 and 2000. Analyses focused on differences in baseline demographic and clinical characteristics and in treatment outcomes between obese and nonobese patients. RESULTS: A total of 35.4% of the patients met criteria for obesity. Significant differences between the obese and nonobese patients were observed for years of education, numbers of previous depressive and manic episodes, baseline scores on the Hamilton Rating Scale for Depression, and durations of the acute episode. A Kaplan-Meier survival analysis indicated a significantly shorter time to recurrence during the maintenance phase among obese patients. The number of patients experiencing a depressive recurrence was significantly higher in the obese than in the nonobese group. CONCLUSIONS: Obesity is correlated with a poorer outcome in patients with bipolar I disorder. Preventing and treating obesity in bipolar disorder patients could decrease the morbidity and mortality related to physical illness, enhance psychological well-being, and possibly improve the course of bipolar illness. Weight-control interventions specifically designed for patients with bipolar illness should be developed, tested, and integrated into the routine care provided for these patients. [ABSTRACT FROM AUTHOR]

Context: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability.Objective: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years.Design: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist.Setting: University-based psychiatric research clinic.Patients: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions.Interventions: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22).Main Outcome Measure: Recurrence of major depressive episode.Results: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years.Conclusion: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of benzodiazepines and zolpidem tartrate in chronic insomnia based on a quantitative review of literature.Data Sources: Articles from 1966 to 1996 were identified using MEDLINE, by a manual review of relevant journals, and from bibliographies of identified articles.Study Selection: Studies using randomized, double-blind, placebo-controlled, parallel or crossover designs with benzodiazepines or zolpidem in adults younger than 65 years with chronic insomnia (modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for primary insomnia) were selected for review. Self-report and polysomnographic measures of sleep-onset latency, total sleep time, number of awakenings, and sleep quality were selected as outcomes.Data Extraction: Twenty-two studies met the selection criteria. A combined test of Pvalues was performed, pooling broadly from the 22 studies to determine whether medication was superior to placebo. A combined test of effect sizes was performed on the subset of studies that reported effect size information to determine the magnitude of medication effect.Data Synthesis: A homogeneous sample of studies summarized 1894 patients treated for a median duration of 7 days. The combined test of P values demonstrated that medication was superior to placebo in all 4 outcome measures. Treatment response was moderate in magnitude by the combined test of effect sizes.Conclusions: Benzodiazepines and zolpidem produced reliable improvements in commonly measured parameters of sleep in patients with chronic insomnia. Relative to the chronic and recurring course of insomnia, both the limited duration of treatments studied and the lack of follow-up data from controlled trials represent challenges for developing evidence-based guidelines for the use of hypnotics in the management of chronic insomnia. [ABSTRACT FROM AUTHOR]

Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS).Method: Subjects included 388 offspring, ages 7-17 years, of 233 parents with BP-I or BP-II (via the Structured Clinical Interview for DSM-IV). Offspring diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Present and Lifetime version (KSADS-PL). Analyses focused on the 41 offspring who were diagnosed with BP-I (N = 9), BP-II (N = 5), or BP-NOS (N = 27).Results: Offspring with BP had proband parents who were significantly younger at the time of their birth, were more likely to be female, and had lower socio-economic status, versus proband parents of offspring without BP. Parental clinical variables and obstetric variables were not significantly associated with BP among offspring. History of physical and/or sexual abuse, exposure to antidepressants, and exposure to stimulants was significantly greater among offspring with versus without BP. There was significantly greater prevalence of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, oppositional defiant disorder/conduct disorder (ODD/CD), and exposure to stimulants and antidepressants among offspring with versus without BP. Variables significantly associated with BP among offspring in regression analyses were as follows: older offspring age, younger parent age at birth, offspring anxiety disorders and ODD/CD, and biological coparent with BP.Conclusion: History of anxiety and/or disruptive behavior disorders, as well as presence of bi-lineal parental BP, is associated with elevated risk of bipolar spectrum disorders among offspring. If replicated prospectively, these findings could have implications for the diagnosis and treatment of psychopathology among BP offspring. [ABSTRACT FROM AUTHOR]

Background: The observation that bipolar disorders frequently go unrecognized has prompted the development of screening instruments designed to improve the identification of bipolarity in clinical and non-clinical samples. Starting from a lifetime approach, researchers of the Spectrum Project developed the Mood Spectrum Self-Report (MOODS-SR) that assesses threshold-level manifestations of unipolar and bipolar mood psychopathology, but also atypical symptoms, behavioral traits and temperamental features. The aim of the present study is to examine the structure of mania/hypomania using 68 items of the MOODS-SR that explore cognitive, mood and energy/activity features associated with mania/hypomania.Methods: A data pool of 617 patients with bipolar disorders, recruited at Pittsburgh and Pisa, Italy was used for this purpose. Classical exploratory factor analysis, based on a tetrachoric matrix, was carried out on the 68 items, followed by an Item Response Theory (IRT)-based factor analytic approach.Results: Nine factors were initially identified, that include Psychomotor Activation, Creativity, Mixed Instability, Sociability/Extraversion, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Inflated Self-esteem, Euphoria, Wastefulness/Recklessness, and account overall for 56.4% of the variance of items. In a subsequent IRT-based bi-factor analysis, only five of them (Psychomotor Activation, Mixed Instability, Spirituality/Mysticism/Psychoticism, Mixed Irritability, Euphoria) were retained.Conclusions: Our data confirm the central role of Psychomotor Activation in mania/hypomania and support the definitions of pure manic (Psychomotor Activation and Euphoria) and mixed manic (Mixed Instability and Mixed Irritability) components, bearing the opportunity to identify patients with specific profiles for a better clinical and neurobiological definition. [ABSTRACT FROM AUTHOR]

Background: Antidepressant drugs can promote remission from acute depressive episodes. Our aim was to establish how long such treatments should be continued to prevent relapse.Method: We did a systematic overview of evidence from randomised trials of continuing treatment with antidepressants in patients with depressive disorders who have responded to acute treatment. Medline, Embase, Cinahl, PsycLIT, Psyndex, and Lilacs were searched.Findings: Data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62-78; 2p<0.00001) compared with treatment discontinuation. The average rate of relapse on placebo was 41% compared with 18% on active treatment. The treatment effect seemed to persist for up to 36 months, although most trials were of 12 months' duration, and so the evidence on longer-term treatment requires confirmation. Significantly more participants allocated antidepressants withdrew from the trials than did those allocated to placebo (18% vs 15%, respectively; odds ratio 1.30, 95% CI 1.07-1.59): the treatment effect could be even greater in adherent patients. The two-thirds reduction in risk of depressive relapse seemed to be largely independent of the underlying risk of relapse, the duration of treatment before randomisation, or the duration of the randomly allocated therapy.Interpretation: Antidepressants reduce the risk of relapse in depressive disorder, and continued treatment with antidepressants would benefit many patients with recurrent depressive disorder. The treatment benefit for an individual patient will depend on their absolute risk of relapse with greater absolute benefits in those at higher risk. Further trials are needed to establish the optimum length of therapy and should include patients who were not well represented in these trials, including those at low risk of relapse. [ABSTRACT FROM AUTHOR]

Background: Mental health treatment is hindered by the limited number of mental health care providers and the infrequency of care. Digital mental health technology can help supplement treatment by remotely monitoring patient symptoms and predicting mental health crises in between clinical visits. However, the feasibility of digital mental health technologies has not yet been sufficiently explored. Rhythms, from the company Health Rhythms, is a smartphone platform that uses passively acquired smartphone data with artificial intelligence and predictive analytics to alert patients and providers to an emerging mental health crisis., Objective: The objective of this study was to test the feasibility and acceptability of Rhythms among patients attending an academic psychiatric outpatient clinic., Methods: Our group embedded Rhythms into the electronic health record of a large health system. Patients with a diagnosis of major depressive disorder, bipolar disorder, or other mood disorder were contacted online and enrolled for a 6-week trial of Rhythms. Participants provided data by completing electronic surveys as well as by active and passive use of Rhythms. Emergent and urgent alerts were monitored and managed according to passively collected data and patient self-ratings. A purposively sampled group of participants also participated in qualitative interviews about their experience with Rhythms at the end of the study., Results: Of the 104 participants, 89 (85.6%) completed 6 weeks of monitoring. The majority of the participants were women (72/104, 69.2%), White (84/104, 80.8%), and non-Hispanic (100/104, 96.2%) and had a diagnosis of major depressive disorder (71/104, 68.3%). Two emergent alerts and 19 urgent alerts were received and managed according to protocol over 16 weeks. More than two-thirds (63/87, 72%) of those participating continued to use Rhythms after study completion. Comments from participants indicated appreciation for greater self-awareness and provider connection, while providers reported that Rhythms provided a more nuanced understanding of patient experience between clinical visits., Conclusions: Rhythms is a user-friendly, electronic health record-adaptable, smartphone-based tool that provides patients and providers with a greater understanding of patient mental health status. Integration of Rhythms into health systems has the potential to facilitate mental health care and improve the experience of both patients and providers., (©C Neill Epperson, Rachel Davis, Allison Dempsey, Heinrich C Haller, David J Kupfer, Tiffany Love, Pamela M Villarreal, Mark Matthews, Susan L Moore, Kimberly Muller, Christopher D Schneck, Jessica L Scott, Richard D Zane, Ellen Frank. Originally published in JMIR Formative Research (https://formative.jmir.org), 07.01.2025.)