Suboptimal adherence to prescribed daily growth hormone regimen among medicaid beneficiaries in the United States.

OBJECTIVE: The objective of this retrospective cohort study was to describe the adherence and discontinuation patterns of somatropin over 3 years among children with pGHD insured by Medicaid across the United States. METHODS: Eligible children were aged ≥3 and <16 years with Medicaid coverage, diagnosed with pGHD, and had ≥2 new prescriptions for somatropin between 1 July 2014 and 31 December 2018. Four non-exclusive patient cohorts were constructed (≥3, 12, 24, and 36 months of continuous enrollment after initial prescription). Suboptimal adherence was defined as medication possession ratio <0.80, and discontinuation as a gap of >60 days between somatropin fills. Logistic and proportional hazards regression methods were used to estimate odds of suboptimal adherence and time to discontinuation, respectively. RESULTS: In the 12-month cohort (n = 3623), mean age was 10.5 ± 3.2 years, 70.8% were male, 44.4% White, 29.1% Hispanic, 7.1% Black, and 1.7% Asian. At months 12, 24, and 36, the proportion with suboptimal adherence was 40.9, 50.4, 54.4%, respectively, and 49.2% of patients with ≥3 months of follow-up discontinued therapy. At 12 months, lower age and race/ethnicity (Black vs. White referent) had greater odds of suboptimal adherence. Discontinuation was associated with Black (vs. White referent) race and geographic region. CONCLUSIONS: Sociodemographic characteristics may be risk factors for suboptimal adherence and/or discontinuation of prescribed somatropin therapy. Improving GH regimen adherence among this at-risk population, and specifically among subgroups at highest risk, is warranted to improve clinical outcomes.

Suboptimal adherence to daily growth hormone in a US real-world study: an unmet need in the treatment of pediatric growth hormone deficiency.

OBJECTIVE: To evaluate adherence to, and discontinuation of, somatropin treatment over 4 years in a US population-based study of children with pediatric growth hormone deficiency (pGHD). METHODS: A retrospective cohort analysis of commercially insured patients ≥3 and <16 years, diagnosed with pGHD, newly treated with somatropin was conducted using Optum De-identified Clinformatics Data Mart. Index date was defined as the first prescription for somatropin between 01 July 2002 and 30 September 2019. Five non-exclusive patient cohorts were identified (>3, 12, 24, 36, and 48 months of post-index continuous enrollment). Suboptimal adherence was defined as medication possession ratio <80%. Discontinuation was defined as the date at which a gap of >60 days between somatropin fills first occurred. Cox proportional hazards regression was used to evaluate time to discontinuation. RESULTS: In the 12-month cohort (n = 3091), mean age was 11.3 ± 2.9 years, 75.9% were male, 70.9% white, 9.4% Hispanic, 3.6% Asian, and 3.1% black. The proportion with suboptimal adherence at months 12 and 48 was 19.6% and 35.9%, respectively. Discontinuation occurred in 42.2% of patients. The rate of discontinuation (HR [95% CI]) was higher for age ≥10 (1.74 [1.53-1.98]), females (1.35 [1.21-1.50]), black and Hispanic race/ethnicity (1.50 [1.18-1.90] and 1.27 [1.09-1.49] compared to White) and obesity (1.69 [1.19-2.40]). CONCLUSION: Suboptimal adherence increases with treatment duration, and risk of discontinuation is associated with age, female gender, black or Hispanic race/ethnicity, and obesity. Strategies that facilitate adherence among children at risk of discontinuation may improve clinical outcomes.

The efficacy of cognitive-behavioral therapy for older adults with ADHD: a randomized controlled trial.

Older adults with ADHD exhibit significant functional impairment, yet there is little research to guide clinicians in evidence-based care of these adults. This study examined response to treatment in older adults who participated in a previous study of the efficacy of cognitive-behavioral treatment (CBT) in adult ADHD. It was hypothesized that older adults would respond less well to CBT than younger adults, given the cognitive demands of the treatment. As described in the original publication, 88 adults who met DSM-IV criteria for ADHD were randomized to receive either a manualized 12-week CBT group intervention targeting executive dysfunction or a parallel Support group. In the current study, outcomes for 26 adults, aged 50 or older, were compared with those of 55 younger adults with respect to inattentive symptoms assessed on a structured interview by a blind clinician, as well as on ratings by self and/or collateral on measures of attention, executive dysfunction, and comorbidity. Contrary to the hypothesis, older and younger adults were equally responsive to CBT on measures of attention. The older adults also responded as well to Support as to CBT on several outcome measures. The results provide preliminary evidence that CBT is an effective intervention for older adults with ADHD. The unexpected response to support highlights a possible age-specificity of effective therapeutic intervention that requires further investigation.

Change in healthcare utilization and costs following initiation of benzodiazepine therapy for long-term treatment of generalized anxiety disorder: a retrospective cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD). While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. METHODS: Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02) who began a long-term course of treatment (≥ 90 days) with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation ("pretreatment" and "post-treatment", respectively), and focused attention on accident-related encounters (e.g., for treatment of fractures) and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness). RESULTS: A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine), while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p<0.01); costs of accident-related encounters and other care that was possibly related to use of benzodiazepines increased by an average of $1099 ($1757 [$7656] vs $2856 [$14,836]; p=0.03). CONCLUSIONS: Healthcare costs increase in patients with GAD beginning long-term (≥ 90 days) treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use.

Medication adherence and utilization in patients with schizophrenia or bipolar disorder receiving aripiprazole, quetiapine, or ziprasidone at hospital discharge: a retrospective cohort study.

BACKGROUND: Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy. METHODS: Using a database linking hospital admission records to health insurance claims, we identified all patients hospitalized for schizophrenia (ICD-9-CM diagnosis code 295.XX) or bipolar disorder (296.0, 296.1, 296.4-296.89) between January 1, 2001 and September 30, 2008 who received aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously enrolled for 6 months before and after hospitalization ("pre-admission" and "follow-up", respectively) were excluded. We examined patterns of use of these agents during follow-up, including adherence with treatment (using medication possession ratios [MPRs] and cumulative medication gaps [CMGs]) and therapy switching. Analyses were undertaken separately for patients with schizophrenia and bipolar disorder, respectively. RESULTS: We identified a total of 43 patients with schizophrenia, and 84 patients with bipolar disorder. During the 6-month period following hospitalization, patients with schizophrenia received an average of 101 therapy-days with the second-generation antipsychotic agent prescribed at discharge; for patients with bipolar disorder, the corresponding value was 68 therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and 37.3% for those with bipolar disorder; approximately one-quarter of patients switched to another agent over this period. CONCLUSIONS: Medication compliance is poor in patients with schizophrenia or bipolar disorder who initiate treatment with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

Healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder: a retrospective cohort study.

BACKGROUND: Patterns of healthcare utilization and costs in patients beginning pharmacotherapy for generalized anxiety disorder (GAD) have not been well characterized. METHODS: Using a large US health insurance database, we identified all patients with evidence of GAD (ICD-9-CM diagnosis code 300.02) who initiated pharmacotherapy with medications commonly used to treat GAD (eg, selective serotonin reuptake inhibitors [SSRIs], venlafaxine, benzodiazepines) between 1/1/2003 and 12/31/2007. We examined healthcare utilization and costs over the 12-month periods preceding and following date of initial receipt of such therapy ("pretreatment" and "follow-up", respectively). Patients with incomplete data were excluded. RESULTS: A total of 10,275 patients met all study inclusion criteria. Forty-eight percent of patients received SSRIs; 34%, benzodiazepines; and 6%, venlafaxine. SSRIs and venlafaxine were about three times more likely to be used on a long-term basis (> 90 days) than benzodiazepines (p < 0.01). In general, levels of healthcare utilization were higher during follow-up than pretreatment. Mean (SD) total healthcare costs increased from $4812 ($10,006) during pretreatment to $7182 ($22,041) during follow-up (p < 0.01); costs of GAD-related pharmacotherapy during follow-up were $420 ($485). CONCLUSIONS: More than one-half of patients initiating pharmacotherapy for GAD receive either SSRIs or venlafaxine. Levels of healthcare utilization and costs are greater in the year following initiation of therapy than in the immediately preceding one.

Outcome assessment of an antipsychotic drug algorithm: effects of the Mississippi State Hospital algorithm project.

OBJECTIVE: This study evaluated a state psychiatric hospital's algorithm for prescribing antipsychotic drugs for inpatients with schizophrenia to determine whether its emphasis on cost efficiency is compatible with quality of care. METHODS: Outcomes were compared for patients who received medication that was algorithm adherent or nonadherent. Risperidone and ziprasidone were first-step oral antipsychotics. Documentation of clinical rationale was acceptable for nonpreferred drug use. Outcomes of interest were length of hospitalization and "much improved" or "very much improved" status on the Clinical Global Impression severity scale (CGI-S). RESULTS: Of 401 patients, 70% were male. The CGI-S modal rating of severity was "markedly ill." Duration of illness was longer for patients given algorithm-nonadherent (17.6±9.7 years) versus -adherent (14.9±11.6 years, p=.013) medication. No statistically significant between-group differences were observed for mean length of stay (51.4±35.5 days versus 43.8±27.4 days, adjusted difference p=.18) or median improvement time (adherent, 41 days; nonadherent, 42 days; CI=34-48 days for both group medians). CONCLUSIONS: Prescription algorithm adherence was not associated with significantly increased length of inpatient stay or delayed time to improvement.

Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naïve patients.

Tardive dyskinesia (TD) rates with second-generation antipsychotics (SGAs) are considered to be low relative to first-generation antipsychotics (FGAs), even in the particularly vulnerable elderly population. However, risk estimates are unavailable for patients naïve to FGAs. Therefore, we aimed to determine the TD incidence in particularly vulnerable, antipsychotic-naïve elderly patients treated with the SGA risperidone or olanzapine. The present work describes a prospective inception cohort study of antipsychotic-naïve elderly patients aged 55 years identified at New York Metropolitan area in-patient and out-patient geriatric psychiatry facilities and nursing homes at the time of risperidone or olanzapine initiation. At baseline, 4 weeks, and at quarterly periods, patients underwent assessments of medical and medication history, abnormal involuntary movements, and extra-pyramidal signs. TD was classified using Schooler-Kane criteria. Included in the analyses were 207 subjects (age: 79.8 years, 70.0% female, 86.5% White), predominantly diagnosed with dementia (58.9%) or a major mood disorder (30.9%), although the principal treatment target was psychosis (78.7%), with (59.4%) or without (19.3%) agitation. With risperidone (n=159) the cumulative TD rate was 5.3% (95% confidence interval (CI): 0.7, 9.9%) after 1 year (mean dose: 1.0±0.76 mg/day) and 7.2% (CI: 1.4, 12.9%) after 2 years. With olanzapine (n=48) the cumulative TD rate was 6.7% (CI: 0, 15.6%) after 1 year (mean dose: 4.3±1.9 mg/day) and 11.1% (CI: 0, 23.1%) after 2 years. TD risk was higher in females, African Americans, and patients without past antidepressant treatment or with FGA co-treatment. The TD rates for geriatric patients treated with risperidone and olanzapine were comparable and substantially lower than previously reported for similar patients in direct observation studies using FGAs. This information is relevant for all patients receiving antipsychotics, not just the especially sensitive elderly.

Toward characterization and definition of fibromyalgia severity.

BACKGROUND: There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities. METHODS: We recruited individuals >or= 18 years of age with a clinician-confirmed diagnosis of FM >or= 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice. RESULTS: The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 +/- 11.0 years, and 81.4% reported duration >or= 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 +/- 2.19 (moderate), and mean sleep interference score was 7.28 +/- 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity. CONCLUSION: With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.

Efficacy of meta-cognitive therapy for adult ADHD.

OBJECTIVE: The authors investigated the efficacy of a 12-week manualized meta-cognitive therapy group intervention designed to enhance time management, organization, and planning in adults with attention deficit hyperactivity disorder (ADHD). METHOD: Eighty-eight clinically referred adults who met DSM-IV criteria for ADHD according to clinical and structured diagnostic interviews and standardized questionnaires were stratified by ADHD medication use and otherwise randomly assigned to receive meta-cognitive therapy or supportive psychotherapy in a group modality. Meta-cognitive therapy uses cognitive-behavioral principles and methods to impart skills and strategies in time management, organization, and planning and to target depressogenic and anxiogenic cognitions that undermine effective self-management. The supportive therapy condition controlled for nonspecific aspects of treatment by providing support while avoiding discussion of cognitive-behavioral strategies. Therapeutic response was assessed by an independent (blind) evaluator via structured interview before and after treatment as well as by self-report and collateral informant behavioral ratings. RESULTS: General linear models comparing change from baseline between treatments revealed statistically significant effects for self-report, collateral report, and independent evaluator ratings of DSM-IV inattention symptoms. In dichotomous indices of therapeutic response, a significantly greater proportion of members of the meta-cognitive therapy group demonstrated improvement compared with members of the supportive therapy group. Logistic regression examining group differences in operationally defined response (controlling for baseline ADHD severity) revealed a robust effect of treatment group (odds ratio=5.41; 95% CI=1.77-16.55). CONCLUSIONS: Meta-cognitive therapy yielded significantly greater improvements in dimensional and categorical estimates of severity of ADHD symptoms compared with supportive therapy. These findings support the efficacy of meta-cognitive therapy as a viable psychosocial intervention.

Reliability, validity, and responsiveness of the daily sleep interference scale among diabetic peripheral neuropathy and postherpetic neuralgia patients.

To evaluate the psychometric characteristics of the Daily Sleep Interference Scale (DSIS) in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), a post hoc secondary analysis of data from eight randomized clinical trials (four DPN and four PHN) was performed. Data were pooled within patient populations when assessment weeks were the same. The DSIS was completed by 1,124 DPN and 1,034 PHN patients. Patient-reported outcomes, including a Daily Pain Diary, the Short-Form McGill Pain Questionnaire, SF-36 Health Survey, Profile of Mood States, MOS-Sleep Scale (MOS-SS), EQ-5D, and Patient Global Impression of Change, were used to validate the DSIS. Test-retest reliability was high for both samples (intraclass correlation coefficient>0.90). The DSIS showed good construct validity, with moderate to high correlations between the DSIS and weekly mean pain scores (r=0.48-0.80), MOS-SS sleep disturbance subscale (r=0.45-0.64), MPQ-SF Pain Experience (r=0.37-0.61), and VAS (r=0.42-0.72). The DSIS showed good discriminant validity in both groups; high and low MOS-SS sleep disturbance groups had significantly different DSIS scores (P<0.001). DPN patients who improved minimally on the Patient Global Impression of Change and in pain scores improved 1.5-2 DSIS points on average; for PHN, patient scores improved an average of 1-2 points. The DSIS demonstrated robust test-retest reliability, good construct and discriminant validity and responsiveness in painful DPN and PHN patients. A 1-2 point change on the DSIS might be interpreted as an important difference.

Clozapine as a first treatment for schizophrenia.

OBJECTIVE: The authors' goal was to explore whether clozapine given as the first antipsychotic treatment favorably affects the course of schizophrenia. METHOD: Thirty-four inpatients experiencing their first episode of schizophrenia or schizoaffective disorder were treated first with clozapine and then followed for up to 4 years. In a previous study, the authors followed patients experiencing their first episode of schizophrenia or schizoaffective disorder who were given fluphenazine as the first treatment. In the current study and the previous study, response criteria required sustained remission of positive symptoms. RESULTS: Nineteen of the 34 subjects met response criteria while taking clozapine. The median time to treatment response was 11 weeks (range=2-13). Using survival analysis, the authors determined that the cumulative response rate for the 34 patients was 66.4% at the end of 13 weeks, which is comparable to the response rate to fluphenazine in the previous study. All responses to clozapine occurred by 13 weeks. Eight (42%) of the clozapine responders discontinued clozapine before 6 months, and only six (32%) remained on clozapine for all of their time in the study. CONCLUSIONS: The authors found no benefit for clozapine over conventional antipsychotics for acute treatment of the first episode of schizophrenia or schizoaffective disorder. Long-term benefits could not be studied because of the high rate of early discontinuation of clozapine treatment.

Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder.

BACKGROUND: Enhancing medication adherence early in the course of schizophrenia and schizoaffective disorder may substantially improve long-term course. Although extensively studied in multi-episode patients, little data exist on medication adherence by first-episode patients. METHOD: Medication adherence was assessed during the first year of treatment and following recovery from the first relapse in patients treated by a standardized medication algorithm. RESULTS: During the first year of treatment, patients with poorer premorbid cognitive functioning were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89; p=0.01), and better executive function decreased the likelihood (hazard ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance medication after a first relapse. CONCLUSION: Interventions to ameliorate cognitive deficits and Parkinsonian side effects may enhance treatment adherence.