Study What You Do: Developing a Psychotherapy Tracking Database in a Large-Scale Integrated Behavioral Health Service.

PURPOSE: Many individuals with behavioral health challenges receive services in primary care, and integrated behavioral health (IBH) programs can help increase access to evidence-based interventions. IBH programs can benefit substantially from integrating standardized tracking databases that allow for the implementation of measurement-based care to evaluate patient-, clinician-, and practice-level outcomes. We describe the development and integration of Mayo Clinic's pediatric and adult primary care psychotherapy tracking database. METHODS: IBH practice leaders directed the development of a large psychotherapy tracking database that continuously populates from Mayo Clinic's electronic health record system. The database captures numerous patient variables including demographics, behavioral health and substance use issues, psychotherapy principles used, and self-reported symptoms. We retrieved current data for patients empaneled in Mayo Clinic's pediatric and adult primary care psychotherapy programs from June 2014 to June 2022. RESULTS: The tracking database contained data for 16,923 adult patients and 6,298 pediatric patients. The mean age of adult patients was 43.2 years (SD 18.3), 88.1% were non-Latine White, and 66.7% identified as female. The mean age of pediatric patients was 11.6 years (SD 4.2), 82.5% were non-Latine White, and 56.9% identified as female. We provide examples of practical applications of the database across clinical, educational, research, and administrative domains. CONCLUSIONS: The development and integration of a psychotherapy tracking database supports clinician communication, examination of patient outcomes, practice quality improvement efforts, and clinically relevant research. Our description of Mayo Clinic's IBH database may serve as a model for other IBH practices.

Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study.

BACKGROUND: The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial. AIMS: The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs. METHODS: Subjects were treated with citalopram/escitalopram for up to 8 weeks. Depression was measured using the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) and the 17-item Hamilton Depression Rating Scale. RESULTS: The group of subjects with at least 1 follow-up visit had a remission (QIDS-C16 ≤ 5) rate of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and 79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study subjects were more likely to achieve a response than STAR*D study subjects. After adjustment for demographic factors, the response rates were not significantly different. When reporting the adverse effect burden, 60.5% of the subjects reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8% reported a moderate-to-severe burden at the 4-week visit. CONCLUSIONS: Patients contemplating initiating an SSRI to treat their MDD can anticipate a high probability of symptom improvement (79.9%) with a low probability that their symptoms will become worse. Patients with lower baseline severity have a higher probability of achieving remission. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study replicates many findings of the first phase of the STAR*D study after controlling for the differences between the studies.

SLC6A4 polymorphisms and age of onset in late-life depression on treatment outcomes with citalopram: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report.

OBJECTIVE: Age at onset of first major depressive episode (MDE) does not necessarily translate into different treatment outcomes to antidepressants in late-life depression. The influence of genetic variants may affect this relationship. DESIGN: Post hoc data set analysis of the association between variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR) of the SCL6A4 gene and treatment outcomes among older participants in the first treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D). SETTING: Participants were enrolled from 23 psychiatric and 18 primary care settings. PARTICIPANTS: Two hundred twenty-one, white non-Hispanic subjects, aged 60 to 75 years, with 16-item Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-CR16) initial score ≥10, and who remained in the study for at least 6 weeks, were genotyped. INTERVENTION: Citalopram treatment for up to 14 weeks. MEASUREMENTS: Main outcome was remission rate defined as a score of ≤5 on the QIDS-CR16. Response was a secondary outcome defined as a reduction of ≥50% of baseline QIDS-CR16. RESULTS: Polymorphism in the indel promoter region was associated with remission among subjects whose first lifetime episode of major depression occurred later than age 55. In this group, subjects with L/L genotype had significantly higher remission (80% versus 43%) compared to those subjects with any other indel promoter genotype. Multivariate analysis demonstrated that the genetic effect of the indel promoter region on remission increases along with age at onset of MDE. CONCLUSIONS: Variants in the indel promoter region of the SLC6A4 gene have a more robust effect to antidepressant outcome among older subjects who experienced their first MDE at a later age. The mechanism of action of these variants remains to be determined.

Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting.

OBJECTIVE: The objective was to evaluate the potential benefit of an integrated, five-gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used to treat major depression in an outpatient psychiatric practice. METHODS: The open-label study was divided into two groups. In the first (unguided) group (n = 113), pharmacogenomic information was not shared until all participants completed the study. In the second (guided) group (n = 114), the pharmacogenomic report was provided to physicians for clinical use. Three depression ratings, the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Quick Inventory of Depressive Symptomatology - Clinician Rated (QIDS-C16), and the Patient Health Questionnaire (PHQ-9), were collected at baseline, and at 2, 4, and 8 weeks. RESULTS: The guided group experienced greater percent improvement in depression scores from baseline on all three depression instruments (HAMD-17, P < 0.0001; QIDS-C16, P < 0.0001; PHQ-9, P < 0.0001) compared with the unguided group. Eight-week response rates were higher in the guided group than in the unguided group on all three measurements (HAMD-17, P = 0.03; QIDS-C16, P = 0.005; PHQ-9, P = 0.01). Eight-week QIDS-C16 remission rates were higher in the guided group (P = 0.03). Participants in the unguided group who at baseline were prescribed a medication that was most discordant with their genotype experienced the least improvement compared with other unguided participants (HAMD-17, P = 0.007). Participants in the guided group and on a baseline medication most discordant with their genotype showed the greatest improvement compared with the unguided cohort participants (HAMD-17, P = 0.01). CONCLUSION: These findings replicate previous studies and demonstrate significantly improved depression outcomes with use of GeneSight, an integrated, multigenetic pharmacogenomic testing platform.

Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

Pretransplant psychiatric and substance use comorbidity in patients with cholangiocarcinoma who received a liver transplant.

BACKGROUND: Psychopathology has been commonly observed in liver transplant candidates, and up to 40% have comorbid psychiatric disorders. This illness burden may negatively impact quality of life and transplant outcome. Liver transplantation for cholangiocarcinoma remains uncommon due to the complex treatment protocol. We assessed for pretransplant psychopathology and substance use disorders in liver transplant recipients with cholangiocarcinoma to better characterize this patient group. METHODS: We retrospectively reviewed the records of 143 liver transplant recipients who completed pretransplant psychological screening with the PAS, BDI-FS, BSI-18, and the SAAST between 2000 and 2004. The majority completed an evaluation by a transplant psychiatrist. Rates of pretransplant psychiatric and substance use symptoms and disorders were compared between 26 patients with cholangiocarcinoma and 117 other liver recipients using χ(2) or Fisher's exact tests. RESULTS: Of the total cohort, 35% had a pretransplant psychiatric diagnosis, 35% had a substance use disorder, and 43% were current or former smokers. The cholangiocarcinoma cohort had significantly lower scores on the PAS, BDI-FS, and the BSI-18. On interview, the cholangiocarcinoma group was less likely to have an alcohol use disorder (P = 0.03) or any substance use disorder (P = 0.04), but the two groups did not differ significantly in the likelihood of having a psychiatric disorder or smoking history. CONCLUSIONS: This study suggests that patients with cholangiocarcinoma have lower rates of alcohol and drug use disorders than other liver transplant recipients. They do not differ in rates of psychiatric disorders or smoking. Psychosocial assessment and support are recommended throughout the transplant process.

Alcohol craving as a predictor of relapse.

BACKGROUND AND OBJECTIVES: Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment. METHODS: The study cohort included 314 alcohol-dependent subjects. Associations between relapse after discharge, PACS score, and clinical variables were investigated using time-to-event analyses. The primary analysis, based on the intent-to-treat principle, presumed relapse in those declining follow-up or not responding to contact attempts. Secondary analysis utilized data from 226 subjects successfully contacted after discharge with a median follow-up time of 365 days. RESULTS: The intent-to-treat analysis demonstrated that relapse was associated with higher level of craving at admission (p= .002) and discharge (p < .001). The analysis of data from patients successfully contacted after discharge led to similar results. A multivariable analysis indicated that relapse rates increased as PACS scores increased, and a higher discharge PACS score was significantly associated with relapse (p= .006) even after adjusting for covariates. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study demonstrates that higher PACS scores at the time of admission and discharge are associated with relapse following residential addiction treatment. These data support the role of craving in relapse and the utility of craving measurement as a clinical guide in assessing relapse risk.

CYP2C19 variation and citalopram response.

OBJECTIVE: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n= 1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P = 0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P = 0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P = 0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.