The impact of a history of child abuse on cognitive performance: a cross-sectional study in older patients with a depressive, anxiety, or somatic symptom disorder.

BACKGROUND: Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a synergistic effect can be assumed in patients with affective symptoms who also have suffered from child abuse. This study examines the association between a history of child abuse and cognitive performance in such patients. METHODS: Cross-sectional data were collected from the 'Routine Outcome Monitoring for Geriatric Psychiatry & Science' project, including 179 older adults (age 60-88 years) with either a unipolar depressive, any anxiety, or somatic symptom disorder referred to specialized geriatric mental health care. A history of physical, sexual, and psychological abuse, and emotional neglect was assessed with a structured interview. Cognitive functioning was measured with three paper and pencils tests (10-words verbal memory test, Stroop Colour-Word test, Digit Span) and four tests from the computerized Cogstate Test Battery (Detection Test, Identification Test, One Card Learning Test, One Back Test). The association between a history of child abuse and cognitive performance was examined by multiple linear regression analyses adjusted for covariates. RESULTS: Principal component analyses of nine cognitive parameters revealed four cognitive domains, i.e., visual-verbal memory, psychomotor speed, working memory and interference control. A history of child abuse was not associated with any of these cognitive domains. However, when looking at the specific types of child abuse separately, a history of physical abuse and emotional neglect were associated with poorer interference control. A history of physical abuse was additionally associated with better visual-verbal memory. CONCLUSIONS: The association between a history of child abuse and cognitive performance differs between the different types of abuse. A history of physical abuse might particularly be a key determinant of cognitive performance in older adults with a depressive, anxiety, or somatic symptom disorder. Future studies on the impact of these disorders on the onset of dementia should take child abuse into account. TRIAL REGISTRATION: ROM-GPS is registered at the Dutch Trial Register ( NL6704 at www.trialregister.nl ).

Subtyping late-life depression according to inflammatory and metabolic dysregulation: a prospective study.

BACKGROUND: Inflammation and metabolic dysregulation are age-related physiological changes and are associated with depressive disorder. We tried to identify subgroups of depressed older patients based on their metabolic-inflammatory profile and examined the course of depression for these subgroups. METHODS: This clinical cohort study was conducted in a sample of 364 depressed older (⩾60 years) patients according to DSM-IV criteria. Severity of depressive symptoms was monitored every 6 months and a formal diagnostic interview repeated at 2-year follow-up. Latent class analyses based on baseline metabolic and inflammatory biomarkers were performed. Adjusted for confounders, we compared remission of depression at 2-year follow-up between the metabolic-inflammatory subgroups with logistic regression and the course of depression severity over 2-years by linear mixed models. RESULTS: We identified a 'healthy' subgroup (n = 181, 49.7%) and five subgroups characterized by different profiles of metabolic-inflammatory dysregulation. Compared to the healthy subgroup, patients in the subgroup with mild 'metabolic and inflammatory dysregulation' (n = 137, 37.6%) had higher depressive symptom scores, a lower rate of improvement in the first year, and were less likely to be remitted after 2-years [OR 0.49 (95% CI 0.26-0.91)]. The four smaller subgroups characterized by a more specific immune-inflammatory dysregulation profile did not differ from the two main subgroups regarding the course of depression. CONCLUSIONS: Nearly half of the patients with late-life depressions suffer from metabolic-inflammatory dysregulation, which is also associated with more severe depression and a worse prognosis. Future studies should examine whether these depressed older patients benefit from a metabolic-inflammatory targeted treatment.

Excess mortality in depressive and anxiety disorders: The Lifelines Cohort Study.

BACKGROUND: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status. METHODS: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models. RESULTS: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty). CONCLUSIONS: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

Impact of childhood trauma on multidimensional frailty in older patients with a unipolar depressive-, anxiety- or somatic symptom disorder.

OBJECTIVES: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty. METHOD: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (≥60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview. RESULTS: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score ≥5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor. CONCLUSION: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research.

Impact of borderline personality disorder traits on the association between age and health-related quality of life: A cohort study in the general population.

BACKGROUND: Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population. METHODS: Cross-sectional data from 5,303 respondents (aged 21-72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders. RESULTS: A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits. CONCLUSION: Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.

Course of frailty stratified by physical and mental multimorbidity patterns: a 5-year follow-up of 92,640 participants of the LifeLines cohort study.

BACKGROUND: The frailty index (FI) is a well-recognized measurement for risk stratification in older people. Among middle-aged and older people, we examined the prospective association between the FI and mortality as well as its course over time in relation to multimorbidity and specific disease clusters. METHODS: A frailty index (FI) was constructed based on either 64 (baseline only) or 35 health deficits (baseline and follow-up) among people aged ≥ 40 years who participated in LifeLines, a prospective population-based cohort living in the Northern Netherlands. Among 92,640 participants, multivariable Cox proportional hazard models were fitted to study the hazard ratio (HR) of the FI at baseline, as well as for 10 chronic disease clusters for all-cause mortality over a 10-year follow-up. Among 55,426 participants, linear regression analyses were applied to study the impact of multimorbidity and of specific chronic disease clusters (independent variables) on the change of frailty over a 5-year follow-up, adjusted for demographic and lifestyle characteristics. RESULTS: The FI predicted mortality independent of multimorbidity and specific disease clusters, with the highest impact in people with either endocrine, lung, or heart diseases. Adjusted for demographic and lifestyle characteristics, all chronic disease clusters remained independently associated with an accelerated increase of frailty over time. CONCLUSIONS: Frailty may be seen as a final common pathway for premature death due to chronic diseases. Our results suggest that initiating frailty prevention at middle age, when the first chronic diseases emerge, might be relevant from a public health perspective.

Clinical effects and treatment outcomes of long-term compulsory in-patient treatment of treatment-resistant patients with severe mental illness and substance-use disorder.

BACKGROUND: The treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder) is difficult and often fails. For patients in the Netherlands who had not responded to earlier voluntary and compulsory treatment, a new treatment facility - Sustainable Residence (SuRe) - was developed to offer long-term compulsory in-patient treatment. AIM OF THE STUDY: To study patterns of changes in clinical and functional outcomes during treatment at SuRe and how these relate to eventual treatment outcome. METHODS: On the basis of the intensity of care needed after four years, three groups of patients were distinguished (total n = 165): those discharged to a less restrictive and less supportive setting (n = 70, 42%), those still hospitalized at SuRe at the end of the four-year study period (n = 69, 42%) and those referred to a more appropriate setting (n = 26, 16%). Random coefficient analysis was used to examine differences between groups regarding changes in clinical and functional outcomes during treatment. During treatment, outcomes were monitored using Routine Outcome Assessment. RESULTS: All three groups made small but significant improvements on global psychosocial functioning, distress and therapeutic alliance (effect sizes (ES) 0.11 to 0.16 per year). Patients who were discharged to a less restrictive setting showed small to moderate improvement in risk to self and others, psychiatric symptoms, and skills for daily living (ES 0.19-0.33 per year and 0.42-0.73 for their mean 2.2-year treatment period). Patients remaining at SuRe showed a small increase in risk to self (ES 0.20 per year; 0.80 for their treatment period of four years or more). Oppositional behaviour was consistently greater in referred patients than in the other groups (ES 0.74-0.75). CONCLUSION: Long-term compulsory treatment appeared to have helped improve clinical and functional outcomes in a substantial proportion (42%) of previously severely dysfunctional, treatment-resistant dual-diagnosis patients, who could then be discharged to a less restrictive and less supportive environment. However, risk-to-self increased in a similar proportion. A smaller number of patients (16%) showed marked oppositional behaviour and needed a higher level of care and protection in another facility.

Prognostic effect of serum BDNF levels in late-life depression: Moderated by childhood trauma and SSRI usage?

BACKGROUND: Brain-derived neurotrophic factor (BDNF) levels decline during depression and normalise after remission, although studies in older patient samples are inconsistent. Whether BDNF serum levels predict depression remission is unclear. We hypothesize that the predictive value of serum BDNF levels in late-life depression is moderated by selective serotonin reuptake inhibitors (SSRI) usage and early traumatization. METHODS: Our study sample was a subset of the Netherlands Study of Depression in Older persons (NESDO), a prospective cohort study. It consisted of 267 older persons with a diagnosis of depression, for which follow-up data were available. Depression diagnosis was assessed at baseline and follow up using a structured diagnostic interview (Composite International Diagnostic Interview (CIDI), volume2.1). Logistic regression was performed (adjusted for covariates) with remission of depression after two years as the dependent variable and baseline BDNF serum levels, childhood traumatization and SSRI use as independent variables. Results - The mean age of the subjects was 70.7 years, 65.6% of them were female, their mean BDNF level was 7.7 ng/ml, 80 (30.0%) of them were traumatised in their childhood,71 (26.6%) used SSRIs and 136 (50.9%) no longer had a depressive disorder at the two year follow up. The predictive value of BDNF serum levels was conditional on traumatization and SSRI usage (threeway interaction p = .010). Higher BDNF serum levels predicted remission in traumatized depressed patients without SSRI usage (OR = 1.17, 95% C.I.: 1.00-1.36; p = .048) and in non-traumatized depressed patients who used SSRIs (OR = 1.17, 95% C.I.: 1.00-1.36; p = .052), but not in the other two subgroups. CONCLUSION: The association between BDNF serum levels and the course of late-life depression seems to depend on SSRI use and childhood trauma. Based on these results, we hypothesize that childhood trauma may permanently reduce ('blunt') the responsiveness of the neurotrophic system to SSRI usage, and that this responsiveness might be more important for depression course than the actual BDNF serum levels.

Group schema-focused therapy enriched with psychomotor therapy versus treatment as usual for older adults with cluster B and/or C personality disorders: a randomized trial.

BACKGROUND: Several types of psychotherapy have been proven successful in the treatment of personality disorders in younger age groups, however studies among older patients are lacking. We developed a group schema-focused therapy (SFT) enriched with psychomotor therapy (PMT) for older adults with cluster B and/or C personality disorders. This paper describes the design of a randomized controlled trial (RCT). We will evaluate the (cost-)effectiveness of this therapy protocol in specialized mental health care. We hypothesize that our treatment program is cost-effective and superior to treatment as usual (TAU) in reducing psychological distress and improving quality of life in older adults treated to specialized mental healthcare. METHODS: A multicenter RCT with a one-year follow-up comparing group schema-focused therapy enriched with psychomotor therapy (group SFT + PMT) and TAU for adults aged 60 years and older who suffer from either a cluster B and/or C personality disorder. The primary outcome is general psychological distress measured with the 53-item Brief Symptom Inventory. Secondary outcomes are the Schema Mode Inventory (118-item version) and the Young Schema Questionnaire. Cost-effectiveness analysis will be performed from a societal perspective with the EuroQol five dimensions questionnaire and structured cost-interviews. DISCUSSION: This study will add to the knowledge of psychotherapy in later life. The study specifically contributes to the evidence on (cost-) effectiveness of group SFT enriched with PMT adapted to the needs of for older adults with cluster b and/or c personality. TRIAL REGISTRATION: Netherlands Trial Register NTR 6621 . Registered on 20 August 2017.

Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age.

AIMS: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. METHODS: Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. RESULTS: Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of loneliness proved to have unique predictive value for a favourable course of depression. Little evidence was found for effect modification by gender or age. CONCLUSIONS: If depressed persons experience difficulties in their social relationships, this may impede their recovery. Special attention for interpersonal problems, social isolation and feelings of loneliness seems warranted in depression treatment and relapse prevention. It will be of great interest to test whether social relational interventions can contribute to better recovery and relapse prevention of depressive disorder.

Metabolic dysregulation and late-life depression: a prospective study.

BACKGROUND: Depression is associated with the metabolic syndrome (MS). We examined whether metabolic dysregulation predicted the 2-year course of clinical depression. METHOD: A total of 285 older persons (⩾60 years) suffering from depressive disorder according to DSM-IV-TR criteria was followed up for 2 years. Severity of depression was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Metabolic syndrome was defined according the National Cholesterol Education Programme (NCEP-ATP III). We applied logistic regression and linear mixed models adjusted for age, sex, years of education, smoking, alcohol use, physical activity, somatic co-morbidity, cognitive functioning and drug use (antidepressants, anti-inflammatory drugs) and severity of depression at baseline. RESULTS: MS predicted non-remission at 2 years (odds ratioper component = 1.26, 95% confidence interval 1.00-1.58), p = 0.047), which was driven by the waist circumference and HDL cholesterol. MS was not associated with IDS sum score. Subsequent analyses on its subscales, however, identified an association with the somatic symptom subscale score over time (interaction time × somatic subscale, p = 0.005), driven by higher waist circumference and elevated fasting glucose level. CONCLUSIONS: Metabolic dysregulation predicts a poor course of late-life depression. This finding supports the concept of 'metabolic depression', recently proposed on population-based findings of a protracted course of depressive symptoms in the presence of metabolic dysregulation. Our findings seem to be driven by abdominal obesity (as indicated by the waist circumference) and HDL cholesterol dysregulation.

Risk assessment and shared care planning in out-patient forensic psychiatry: cluster randomised controlled trial.

BACKGROUND: Forensic psychiatry aims to reduce recidivism and makes use of risk assessment tools to achieve this goal. Various studies have reported on the predictive qualities of these instruments, but it remains unclear whether their use is associated with actual prevention of recidivism in clinical care. AIMS: To test whether an intervention combining risk assessment and shared care planning is associated with a reduction in violent and criminal behaviour. METHOD: A cluster randomised controlled trial (Netherlands Trial Register number NTR1042) was conducted in three out-patient forensic psychiatric clinics. The intervention comprised risk assessment with the Short Term Assessment of Risk and Treatability (START) and a shared care planning protocol formulated according to shared decision-making principles. The control group received usual care. The outcome consisted of the proportion of clients with violent or criminal incidents at follow-up. RESULTS: In total 58 case managers and 632 of their clients were included. In the intervention group (n = 310), 65% received the intervention at least once. Findings showed a general treatment effect (22% of clients with an incident at baseline v. 15% at follow-up, P<0.01) but no significant difference between the two treatment conditions (odds ratio (OR) = 1.46, 95% CI 0.89-2.44, P = 0.15). CONCLUSIONS: Although risk assessment is common practice in forensic psychiatry, our results indicate that the primary goal of preventing recidivism was not reached through risk assessment embedded in shared decision-making.

Depression after myocardial infarction is a risk factor for declining health related quality of life and increased disability and cardiac complaints at 12 months.

OBJECTIVE: To study the prospective effects of post-myocardial infarction (MI) depressive disorder on health status, including self reported cardiac symptoms, disability, and health related quality of life, at 12 months after MI while controlling for cardiac condition and health status at three months after MI. METHODS: Longitudinal study of a cohort of 468 adults with MI recruited from four hospitals in the north of The Netherlands between September 1997 and September 2000. Assessment of depressive disorder in the year after MI according to International classification of disease, 10th revision criteria. Assessment of health status at three and 12 months by the RAND 36 item health survey, the health complaints scale, self rated cardiac complaints, and disability. RESULTS: Patients with post-MI depressive disorder were more likely than those without to have poor quality of life, more health complaints, more cardiac complaints, and more disability at 12 months' follow up. In multivariate analyses adjusted for cardiac condition, health status at three months, age, sex, and pre-MI depression, the prospective association of post-MI depression with poor health status remained for most of the indicators. Severity of the post-MI depression further contributed to aspects of poor health status. CONCLUSIONS: In a prospective study design, post-MI depression had strong effects on poor health status exceeding the effects of cardiac condition and its short term consequences. Efforts to improve health status after MI should therefore include standard assessment and guideline based treatment of post-MI depressive disorder.

Depression as an independent determinant of decreased heart rate variability in patients post myocardial infarction.

OBJECTIVE: Depression is associated with an increased risk of cardiac morbidity and mortality in patients following myocardial infarction (MI). Our objective was to investigate the potential role of the autonomic nervous system in mediating this detrimental effect. METHODS: The study group consisted of 95 consecutive post-MI patients without depression and 53 post-MI patients with depression. Depressive symptoms were assessed by the Beck Depression Inventory (BDI). Activity of the autonomic nervous system was assessed by analysing heart rate variability (HRV) using 24-hour ambulatory electrocardiographic recordings as obtained three months post MI. RESULTS: Higher age, female gender and left ventricular ejection fraction <0.40 were associated with lower HRV (SDANN, and very-low-frequency and low-frequency power, but not RMSSD and high-frequency power), as was depression. In the multivariate analysis, age and left ventricular ejection fraction but not gender emerged to be independently associated with HRV. After adjustment for these two covariates, depression remained significantly associated with low HRV. CONCLUSIONS: Patients with depression in the present post-MI study are characterised by decreased longer-range HRV compared with the patients without depression, independent of other clinical variables. This observation supports the concept that one of the mechanisms underlying the detrimental effect of depression on post-MI prognosis may be that depression adds to the autonomic derangement post MI.

Help-seeking behaviour of hearing-impaired persons aged > or = 55 years; effect of complaints, significant others and hearing aid image.

OBJECTIVE: To determine factors influencing help-seeking behaviour in hearing-impaired persons aged > or = 55 years MATERIAL AND METHODS: The study comprised 1,419 persons (480 females, 939 males) aged > or = 55 years who participated voluntarily in a driving test. Pure-tone audiometry was performed in all subjects. Participants without a hearing aid with an average hearing loss of > or = 30 dB in the better ear for the frequencies 0.5, 1, 2 and 4 kHz were asked how they perceived their hearing by means of a structured questionnaire. The questionnaire provided insight into why some hearing-impaired people seek help from a general practitioner (GP) and others do not. Four factors were examined. RESULTS: A total of 483/1.419 (34%) participants tested had a hearing loss exceeding 30 dB. Fewer than half of these had visited their GP with complaints of hearing impairment. Of those who had not sought help from a GP, 57% nevertheless judged their hearing as poor. Social pressure exerted by significant others was less in the non-consulters group. Hearing aid image did not differ significantly between the two groups. CONCLUSION: The help-seeking behaviour of hearing-impaired elderly people is related to the degree of hearing disability and the social pressure exerted by significant others as well as the willingness to try hearing aids.

Effects on depression pharmacotherapy of a Dutch general practitioner training program.

BACKGROUND: General practitioners' (GPs) ability to recognize, diagnose and treat depression improved significantly after a comprehensive, 20-h training programme. This study aims to evaluate in more detail the effects of the training on GPs' pharmacotherapy of depression and related issues. METHODS: A pretest-posttest design was used. Both in the pre- and post-training phase, a sample was drawn from consecutive patients of the 17 participating GPs. In the pre-training phase we identified a sample of 31 cases with an ICD-10 depression who received an antidepressant from their GP. The sample was followed for 1 year. Outcome measures were: type of antidepressant, dosage, duration and number of target instructions given by the GP. Then we trained the GPs. In the post-training phase, we identified a new sample (n = 47) from their practices and measured the same outcomes. RESULTS: Improvements were seen in choice for modern antidepressant, adequate dosage, adequate duration, and number of target instructions given. LIMITATIONS: Observed changes can be due to a period effect, inherent in a pre-post design. CONCLUSIONS: A post-academic hands-on training of GPs can improve depression pharmacotherapy according to clinical guidelines with respect to choice of a modern antidepressant, adequate dosage, adequate duration and psychoeducation.