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Biomedical subjects

Roger S McIntyre

Publications and source records attributed to Roger S McIntyre.

At least 37 records · Page 2Linked to original sources

Open-label adjunctive topiramate in the treatment of unstable bipolar disorder.

OBJECTIVE: To assess open-label adjunctive topiramate in the treatment of outpatients with unstable bipolar disorder (BD). METHOD: Outpatients with DSM-IV-defined BD (I or II) exhibiting mood instability were enrolled in this 16-week, open-label, multicentre study. Topiramate was added to existing mood stabilizers and other psychotropic treatments. The primary effectiveness measure was the Clinical Global Impression of Severity (CGI-S) scale; other scales included the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). Safety assessments included monitoring adverse events, measuring tremor, monitoring vital signs and weight, and laboratory indices. We also evaluated patient satisfaction with treatment. RESULTS: A total of 109 patients were enrolled. Intent-to-treat analysis showed significant improvement from baseline in the CGI-S, YMRS, and MADRS, starting at Week 2 (P < 0.001), with further accrual of benefit between Week 2 and Week 16 (P < 0.001). The mean modal dosage of topiramate during the stable dosing period was 180 mg daily. There was a mean 1.8 kg decrease in patient weight from topiramate initiation to Week 16 (P < 0.001). Topiramate was well tolerated by most patients; 11% withdrew from the study owing to adverse events. We noted a significant reduction in the mean severity score for preexisting tremor by Week 8 of treatment (P < 0.005); no notable changes in vital signs were observed. At Week 16, 50% of the patients were "completely satisfied" with topiramate treatment. CONCLUSIONS: Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II.

Adult↗

Atypical antipsychotics in psychiatric practice: practical implications for clinical monitoring.

OBJECTIVES: To provide practical recommendations for monitoring patients both before and during treatment with atypical antipsychotics, to assist clinicians in implementing preventative measures against diabetes, and to establish baselines according to which clinicians should initiate diabetes treatment. METHOD: A working group of Canadian specialists in psychiatry and endocrinology reviewed peer-reviewed clinical studies published in this area and other relevant papers and abstracts. RESULTS: The reviewed studies further confirm that atypical antipsychotic medications are the most effective components in the medical management of many psychotic conditions; they also further emphasize the need to more stringently monitor and recognize diabetes risk factors inherent in these patients. Recommendations are based on a review of the available data, on expert opinion and consensus, and on current Canadian guidelines for the treatment of schizophrenia and management of diabetes. CONCLUSIONS: Patients with psychiatric disorders, most particularly schizophrenia and mood disorders, have an increased risk for type 2 diabetes and should be screened frequently, especially when other risk factors are present. The resulting recommendations offer practical steps for effectively screening patients prior to and during treatment with atypical antipsychotics. They include (1) how to conduct an initial baseline assessment, (2) when and how to monitor blood glucose and lipid levels, and (3) how to educate patients regarding such lifestyle issues as nutrition, exercise, and diet.

Antipsychotic Agents↗

Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms.

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine's symptom-alleviating effect on the somatic dimension of depressive illness.

Antidepressive Agents↗

Tolerability profiles of atypical antipsychotics in the treatment of bipolar disorder.

Atypical antipsychotics have unequivocally advanced the pharmacotherapy of bipolar disorder. These broad-spectrum medications offer efficacy against core symptoms of mania, and evidence supports the use of several agents as treatment options in depressed and maintenance phases of the disorder. Atypical antipsychotics also have a reduced propensity for provoking acute or tardive neurologic adverse events compared with their therapeutic predecessors, the conventional antipsychotics. These agents are not, however, a panacea and are associated with several problematic tolerability and safety concerns. Although classified together, atypical antipsychotics are heterogeneous in their tolerability and safety profiles, an issue that is relevant to individualizing treatment selection. This article reviews relevant adverse events attributable to the use of atypical antipsychotic agents, with particular consideration of the bipolar disorder population.

Antipsychotic Agents↗

Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?

Contemporary mechanistic models of several psychiatric disorders propose abnormalities in the structure and function of distinct neural networks. The cerebellum has both anatomic and functional connections to the prefrontal cortex, the subcortical limbic structures and monoamine-producing brainstem nuclei. Conspicuously, however, the cerebellum has been underemphasized in neuropsychiatric research. A growing confluence of scientific data indicate that the cerebellum may not be irrelevant, which suggests that an integrated model of neuropsychiatric disorders should include a role for the cerebellum and its relevant neural connections. This review summarizes the published data describing and characterizing the putative role of the cerebellum in normal and abnormal mood regulation, with specific attention to states of psychosis, depression and mania. The available evidence suggests that a functional role for the cerebellum should be considered in future neuropsychiatric studies.

Bipolar Disorder↗

The antidepressant effects of risperidone and olanzapine in bipolar disorder.

OBJECTIVE: To describe the antidepressant effectiveness of olanzapine and risperidone and compare their tolerability when employed adjunctively in bipolar I/II disorder. METHOD: In an observational study, twenty-one ambulatory subjects with DSM-IV defined bipolar I/II disorder, in any phase of the illness, openly received adjunctive risperidone or olanzapine. The primary efficacy parameters were the Hamilton Depression Rating Scale (HDRS-17) and the Maier and Philips Severity Subscale. Secondary efficacy parameters included the Young Mania Rating Scale (YMRS) along with the Clinical Global Impressions Scale (CGI). Response was defined as a significant change from baseline to endpoint in the total mean HDRS-17 score. The primary tolerability parameters were the Abnormal Involuntary Movement Scale (AIMS) along with changes in weight and body mass index (BMI-kg/m2). Patients were evaluated prospectively with repeated monthly assessments for up to 6 months. RESULTS: Eleven patients openly received risperidone; 10 received olanzapine adjunctive to either lithium or divalproex. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p=0.001), with the mean HDRS-17 total scores falling from 17(SD=3.2) to 5(SD=1.5) by 6 months in the risperidone-treated group and from 18 (SD=1.9) to 7 (SD=2.0) in the olanzapine-treated group. Differences between the risperidone-treated group and the olanzapine-treated group were not significant at 6 months (p=0.754). The mean doses of study medication were 2.88 (SD=1.6) mg/day for the risperidone-treated group and 12.69 (SD=2.3) mg/day for the olanzapine-treated group. Both risperidone and olanzapine were generally well tolerated. No patients developed tardive dyskinesia. Significant weight gain was experienced by patients in both groups [mean weight gain at endpoint was 5.9 kg in risperidone (p=0.023) and 11.3 kg in olanzapine (p=0.001)]. There was a significant difference in weight gain between the risperidone-treated group and the olanzapine-treated group (p=0.001). CONCLUSIONS: These pilot data, from the first prospective comparison study of risperidone and olanzapine in bipolar disorder, suggest that adjunctive administration of either agent may reduce depressive symptom severity. No subjects receiving risperidone or olanzapine developed tardive dyskinesia. Both compounds imparted substantial weight gain with significantly more weight gain accrual with olanzapine. As this was an observational study, the antidepressant effect and tolerability profile of these compounds requires validation via double-blind placebo controlled investigations.

Adolescent↗

Comorbidity in bipolar disorder: a framework for rational treatment selection.

Bipolar disorders are heterogeneous disorders often requiring multimodality treatment. The expanding pharmacopeia for bipolar disorders invites the need for a treatment framework that both recognizes and anticipates the multidimensionality and comorbidity of the illness. No available neurotherapeutic agent is singularly efficacious for the complete mélange of bipolar symptomatology. An apparent paradox has emerged in the management of bipolar disorder; whilst results from rigorous controlled monotherapy trials suggest that a disparate assortment of neurotherapeutic agents are efficacious in distinct phases of bipolar disorder, the majority of tertiary-treated bipolar patients receive polypharmacotherapeutic regimens. The evidentiary base for polypharmacotherapy is sparse and has recently become an area of active research focus. In the interim, clinicians are encouraged to invoke an organizational schema for the treatment of bipolar disorder that considers the spectrum of effectiveness of putative and established mood stabilizers. This schema should be further informed by the treatment data for comorbid and accessory conditions. The authors propose a schema to provide the impetus for further work in the area.

Antimanic Agents↗

Bipolar disorder: a national health concern.

Bipolar disorders are prevalent, disabling, and costly diseases that often pursue an inexorable course. Underdetection, misdiagnosis, and diagnostic delay frequently and unnecessarily interfere with appropriate treatment of the disorder. Mortality studies in bipolar disorder underscore the relevance of both unnatural and natural causes of death, inviting the need for improved preventative and primary health care for bipolar patients. The treatment framework for bipolar disorder must recognize and anticipate the multidimensionality and comorbidity of this illness. Pharmacotherapy is necessary, with multiple concomitant medications required for most patients. In addition, adjunctive psychosocial interventions offer enhanced compliance and may beneficially influence psychopathological and functional outcomes. This article emphasizes the public health concern of bipolar disorder, and provides tactics to enhance detection of cryptic bipolar states, underscore the clinical and pathophysiological relevance of comorbidity in bipolar disorder, and provide a framework for multimodality therapy for this condition.

Adult↗

The human cost of not achieving full remission in depression.

Depression is among the most disabling and costly illnesses in the world. Despite good short-term efficacy outcomes in the treatment of depression, long-term outcomes remain disappointing. Depression continues to be missed or underdiagnosed and undertreated, and comorbidities are frequently not identified. Of particular concern is the low rate of depression treated to full remission. Treating only to response leaves patients with residual depressive symptoms and an increased risk of a recurrent or chronic course. Anything less than full remission should be considered a treatment failure. This article examines the substantial psychiatric, medical, functional, and economic costs associated with not achieving remission. Available pharmacoeconomic data and randomized, controlled clinical trials published in the last 5 years identified through Medline searches with terms including burden, cost, economics, serotonin reuptake inhibitors (also, specific agents), venlafaxine, nefazadone, mirtazapine, psychotherapy, remission, and depression were reviewed. One of the limiting factors to this review is that few trials have compared the effects of various antidepressant strategies on clinically relevant outcomes such as depression-free days and patient productivity, making the full benefit of remission more difficult to measure. Patients who fail to achieve a full remission have a more recurrent and chronic course, increased medical and psychiatric comorbidities, greater functional burden, and increased social and economic costs. Cost-effective treatment for depression includes antidepressant therapies with higher remission rates. Antidepressants with a dual mechanism of action and combination therapies are associated with higher remission rates, more depression-free days, reduced pain-symptom morbidity, reduced health service utilization, and improved productivity.

Achievement↗

Treating bipolar disorder. Evidence-based guidelines for family medicine.

OBJECTIVE: To provide an evidence-based summary of medications commonly used for bipolar disorders and a practical approach to managing bipolar disorders in the office. QUALITY OF EVIDENCE: Articles from 1990 to 2003 were selected from MEDLINE using the key words "bipolar disorder," "antiepileptics," "antipsychotics," "antidepressants," and "mood stabilizers." Good-quality evidence for many of these treatments comes from randomized trials. Lithium, divalproex, carbamazepine, lamotrigine, oxcarbazepine, and some novel antipsychotics all have level I evidence for treating various aspects of the disorder. MAIN MESSAGE: Treatment of bipolar disorder involves three therapeutic domains: acute mania, acute depression, and maintenance. Lithium has been a mainstay of treatment for some time, but antiepileptic drugs like divalproex, carbamazepine, and lamotrigine, along with novel antipsychotic drugs like olanzapine, risperidone, and quetiapine, alone or in combination, are increasingly being used successfully to treat acute mania and to maintain mood stability. CONCLUSION: Bipolar disorder is more common in family practice than previously believed. Drug treatments for this complex disorder have evolved rapidly over the past decade, radically changing its management. Treatment now tends to be very successful.

Algorithms↗

An approach to managing depression. Defining and measuring outcomes.

OBJECTIVE: To provide family physicians with a contemporary approach to formulating a treatment model for major depressive disorder that integrates definitions of new therapeutic end points, familiarizes them with tools for assessing these end points, and describes newer methods for enhancing outcome. SOURCES OF INFORMATION: Canadian Psychiatric Association Guidelines for the Treatment of Depressive Disorders, relevant articles from a MEDLINE search using the MeSH headings"full remission" and "depression," and the authors' clinical experience. MAIN MESSAGE: Major depressive disorder is an episodic, relapsing, and sometimes chronic illness. Depressive symptoms in primary care settings are often vague reports of anhedonia, anxiety, and nonspecific somatic complaints. Therapeutic objectives in depression are full remission of depressive symptoms, prevention of recurrence, and restoration of function. Depression rating scales can be useful for monitoring and treating depression. CONCLUSION: The proposed therapeutic model anticipates the chronic course of illness, defines treatment end points, encourages longer duration of treatment, and includes both pharmacologic and lifestyle therapies. The 7-item Hamilton Depression Rating Scale can assist clinicians in determining when full remission has occurred.

Antidepressive Agents↗

Valproate, bipolar disorder and polycystic ovarian syndrome.

BACKGROUND: Persons with bipolar disorder are often overweight and cluster risk factors for cardiovascular disease. Some antibipolar agents adversely impact upon weight and the lipid milieu. Recent data suggest that valproic acid, a commonly prescribed mood stabilizer, may be associated with polycystic ovarian syndrome (PCOS). This adverse event has not been systematically studied in bipolar disorder. METHOD: Thirty-eight female subjects, aged 18-50 years, meeting DSM-IV criteria for bipolar I or II disorder, in any phase of illness were evaluated. Eighteen females received valproate (sodium valproate and valproic acid) and 20 females received lithium. Patients completed questions regarding their menstrual, reproductive and medical histories. During the follicular phase they were assessed for weight, body mass index (BMI kg/m2), and changes in the reproductive endocrine milieu that included morning estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone binding globulin (SHBG), androstenedione, dehydroepiandrosterone-sulfate (DHEAS), testosterone, free testosterone, prolactin and thyroid-stimulating hormone (TSH). The blood was also analyzed for fasting metabolic parameters which included total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin, glycosylated hemoglobin (HbA1C), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding-protein 1 (IGFBP-1), fasting blood glucose and morning leptin. RESULTS: Nine (50%) of the valproate-treated females had menstrual abnormalities versus three (15%) of the lithium-treated females (p < 0.05). Valproate-treated females had significantly higher levels of follicular phase androgen concentrations than lithium-treated females (p < 0.05). Nine (50%) of females who were overweight (BMI > or = 25 kg/m2) and with a history of menstrual irregularities also exhibited laboratory evidence of hyperandrogenism (p < 0.05). Persons receiving valproate exhibited significant increases in fasting biochemical parameters suggestive of an adverse metabolic syndrome (p < 0.05). Leptin levels were significantly elevated in the valproate-treated females (p < 0.05). CONCLUSIONS: In this pilot, open-label cross-sectional study, valproate-treated females exhibited higher rates of menstrual abnormalities and biochemical evidence of both hyperandrogenism and adverse metabolic parameters when compared with lithium-treated females. These preliminary data suggest that valproate may, in some predisposed females, adversely impact upon the reproductive endocrine milieu and result in aspects of the metabolic syndrome.

Adolescent↗

Antipsychotic-induced weight gain: bipolar disorder and leptin.

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Adolescent↗

Risk of weight gain associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain occurs in a substantial percentage of treated persons. There remains a paucity of naturalistic data that describe relative weight-gain liability with the available novel atypical antipsychotics (NAPs). This investigation describes comparative NAP-induced weight gain in a prospective naturalistic cohort of persons with schizophrenia and related psychotic disorders. METHODS: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is an ongoing prospective, longitudinal, naturalistic study involving 32 academic and community sites across Canada. Persons with DSM-IV-defined schizophrenia, schizophreniform or schizoaffective disorder, and psychosis not otherwise specified were consecutively enrolled. The overarching objectives of this initiative were to collect and compare global effectiveness, tolerability, safety, and humanistic outcomes in persons receiving commercially available NAPs in Canada. This analysis reports only weight change with the respective NAPs. Other outcomes were reported in separate companion papers. RESULTS: A spectrum of weight-gain liability was noted with quetiapine (QUE) (mean 7.55 kg, SD 9.20; P = 0.28), olanzapine (OLZ) (mean 3.72 kg, SD 0.56; P = 0.15), and risperidone (RIS) (mean 1.62 kg, SD 7.72; P = 0.43). Categorically defined weight gain (that is, over 7% of baseline weight) was observed in 55.6% of QUE patients, 24.1% of OLZ patients, and 23.7% of RIS patients. Adjusting for demographic and disease-specific confounding factors, QUE patients had greater odds of gaining over 7% of their baseline weight compared with RIS patients (odds ratio [OR] 3.62; 95% CI, 1.02 to 12.83; P = 0.05). No statistical difference was detected between OLZ patients and RIS patients for over 7% of baseline weight (OR 1.54; 95% CI, 0.63 to 3.75; P = 0.12) or over 10% weight gain (OR 1.44; 95% CI, 0.50 to 4.13; P = 0.58). CONCLUSION: Clinicians are reminded to monitor anthropometric and metabolic parameters in all NAP-treated persons. Clinically significant differences in weight gain liability exist among the available NAPs.

Adult↗

What to do if an initial antidepressant fails?

OBJECTIVE: To provide family physicians with practical ways of managing depressed patients responding insufficiently to initial antidepressant treatment. QUALITY OF EVIDENCE: A search of MEDLINE and relevant bibliographies showed most studies could be categorized as level III evidence. Few well controlled studies (eg, level I evidence) specify treatment of next choice in rigorously defined treatment-refractory depression (TRD). MAIN MESSAGE: Failure to achieve and sustain full symptom remission affects relatively few treated depressed patients. Most chronically depressed people are not absolutely resistant but are relatively resistant to treatment; they fail to achieve the goals of treatment because of improper diagnosis or insufficient treatment application. The literature on TRD has largely focused on medication strategies; fewer studies investigated psychosocial approaches. The best established augmentation strategies are lithium salts and triidothyronine (T3). Combination antidepressants have become clinical psychiatrists' preferred treatment, despite limited evidence. Electroconvulsive therapy (ECT) remains a feasible option for TRD, but response rates are poor among people with TRD. High relapse rates after ECT remain a serious and common clinical dilemma. CONCLUSION: Family physicians should familiarize themselves with some new strategies to modify inadequate response to initial antidepressant treatment.

Algorithms↗

Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study.

OBJECTIVE: Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. METHODS: A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method. RESULTS: The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 0.043, respectively]. CONCLUSIONS: These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.

Acute Disease↗

Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.

BACKGROUND: This study was designed to evaluate the effect of combining bupropion sustained release (SR) with venlafaxine, paroxetine, or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents. METHOD: Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (a serotonin-norepinephrine reuptake inhibitor), eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing. RESULTS: There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (chi2= 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08; women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6.89, df = 4,24; p = .001) accompanied by a decrease in O-desmethylvenlafaxine (F = 14.26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial. CONCLUSION: Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs. Further investigation of combination treatments under randomized, double-blind conditions is recommended.

Adult↗