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1.
J Clin Psychopharmacol ; 34(3): 313-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24743713

ABSTRACT

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.


Subject(s)
Citalopram/therapeutic use , Depressive Disorder, Major/drug therapy , Pharmacogenetics , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/therapeutic use , Citalopram/adverse effects , Depressive Disorder, Major/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/adverse effects , Severity of Illness Index , Treatment Outcome
2.
Pharmacogenet Genomics ; 23(10): 535-48, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24018772

ABSTRACT

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.


Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Pharmacogenetics/methods , Adult , Aged , Aryl Hydrocarbon Hydroxylases/genetics , Citalopram/therapeutic use , Cohort Studies , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP2C19 , Cytochrome P-450 CYP2D6/genetics , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Outpatients , Psychiatric Status Rating Scales/standards , Treatment Outcome , Young Adult
3.
Pharmacogenet Genomics ; 21(1): 1-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21192344

ABSTRACT

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.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Citalopram/therapeutic use , Depression/drug therapy , Depression/genetics , Genetic Variation/physiology , Adolescent , Adult , Aged , Algorithms , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/therapeutic use , Aryl Hydrocarbon Hydroxylases/physiology , Citalopram/adverse effects , Cytochrome P-450 CYP2C19 , Depression/diagnosis , Depression/ethnology , Drug Tolerance/genetics , Female , Gene Frequency , Genetic Association Studies , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Remission Induction , Treatment Outcome , Young Adult
4.
Psychiatry Res ; 129(3): 293-5, 2004 Dec 30.
Article in English | MEDLINE | ID: mdl-15661324

ABSTRACT

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.


Subject(s)
Anxiety/diagnosis , Depressive Disorder/diagnosis , Depressive Disorder/therapy , Electroconvulsive Therapy/methods , Somatoform Disorders/diagnosis , Adult , Anxiety/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Remission Induction , Severity of Illness Index , Somatoform Disorders/epidemiology , Surveys and Questionnaires , Treatment Outcome
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