developments in depression timothy dellenbaugh, md asssociate professor of psychiatry psychiatry...

Developments in Developments in DepressionDepression

Timothy Dellenbaugh, MDTimothy Dellenbaugh, MD

Asssociate Professor of Asssociate Professor of PsychiatryPsychiatry

Psychiatry Residency DirectorPsychiatry Residency Director

UMKCUMKC

TopicsTopics

• GeneticsGenetics

• Natural Hx and risk factorsNatural Hx and risk factors

• Service DeliveryService Delivery

• Suicide RiskSuicide Risk

• TreatmentTreatment

PretestPretest

Genetic Linkage for depression Genetic Linkage for depression has been reported for which has been reported for which chromosomeschromosomes

A.A. 88

B.B. 1111

C.C. 1313

D.D. 1515

E.E. 1717

F.F. 2222

G.G. All of the aboveAll of the above

Individuals with which polymorphism Individuals with which polymorphism of the of the HTR2A HTR2A gene (13) were NOT gene (13) were NOT responsive to the protective aspects of responsive to the protective aspects of nurturing motheringnurturing mothering

A.A. T/TT/T

B.B. T/CT/C

C.C. C/CC/C

When there were No reported adversities, When there were No reported adversities, the risk of adolescent depression was the the risk of adolescent depression was the same between low birth weight and normal same between low birth weight and normal weight femalesweight females

A.A. TrueTrue

B.B. FalseFalse

Individuals with late life onset Individuals with late life onset depression had greater depression had greater impairment than early onsetimpairment than early onset

A.A. TrueTrue

B.B. FalseFalse

The decrease in antidepressant The decrease in antidepressant utilization after the FDA Advisory was utilization after the FDA Advisory was offset by increased use of other offset by increased use of other medicationsmedications

A.A. TrueTrue

B.B. FalseFalse

After the FDA advisory, patients started on After the FDA advisory, patients started on antidepressants received closer follow-up as antidepressants received closer follow-up as recommendedrecommended

A.A. TrueTrue

B.B. FalseFalse

When patients had equal mood reactivity to When patients had equal mood reactivity to sad mood provocation, their relapse risk was sad mood provocation, their relapse risk was lower if they had been treated with CBT lower if they had been treated with CBT instead of antidepressantsinstead of antidepressants

A.A. TrueTrue

B.B. FalseFalse

High density negative-ion therapy High density negative-ion therapy was just as effective as light therapy was just as effective as light therapy for seasonal affective disorderfor seasonal affective disorder

A.A. TrueTrue

B.B. FalseFalse

GeneticsGenetics

Genetics of Recurrent Genetics of Recurrent Early-Onset Major Early-Onset Major DepressionDepression• Am J Psychiatry 2007; 164:248–258Am J Psychiatry 2007; 164:248–258• DNA markers were studied in 656 families with two or more cases DNA markers were studied in 656 families with two or more cases • (onset before age 31 in probands and age 41 in other relatives)(onset before age 31 in probands and age 41 in other relatives)• Genomewide suggestive evidence for linkage was observed on Genomewide suggestive evidence for linkage was observed on

chromosome 15q25-q26 chromosome 15q25-q26 • In the secondary analysis, suggestive linkage results were In the secondary analysis, suggestive linkage results were

observed on chromosome 17p12 (28.0 cM,excess sharing in male-observed on chromosome 17p12 (28.0 cM,excess sharing in male-male and male-female pairs) male and male-female pairs)

• and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs).male-male pairs).

• Conclusions: Conclusions: These regions of chromosomes 15q, 17p, and 8p These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major might contain genes that contribute to susceptibility to major depression and related disorders.depression and related disorders.

• Evidence for linkage has been reported independently in the Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.chromosome 8p for related personality traits.

Genetic Variation in SuicideGenetic Variation in Suicideand Major Depressionand Major Depression

• Arch Gen Psychiatry. 2006;63:35-48Arch Gen Psychiatry. 2006;63:35-48

• Chromosome 22 Chromosome 22

• Spermine is stored in synaptic vesicles and Spermine is stored in synaptic vesicles and released by depolarization neurotransmittersreleased by depolarization neurotransmitters

• Impacts effects of lithiumImpacts effects of lithium

• Impacts serotonin reuptakeImpacts serotonin reuptake

• SSAT (spermine/spermidine SSAT (spermine/spermidine NN1-1-acetyltransferase), may play a role in the acetyltransferase), may play a role in the predisposition to suicide and major depressionpredisposition to suicide and major depression

Genetic Markers of Suicidal Ideation Genetic Markers of Suicidal Ideation Emerging DuringEmerging DuringCitalopram Treatment of Major Citalopram Treatment of Major DepressionDepression

• Am J Psychiatry 2007; 164:1530–1538Am J Psychiatry 2007; 164:1530–1538

• DNA samples from 1,915 participants DNA samples from 1,915 participants were genotyped for 768 single-nucleotide were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genespolymorphisms in 68 candidate genes

• genes GRIA3 (chromosome X)genes GRIA3 (chromosome X)• And GRIK2 (Chromosome 6)And GRIK2 (Chromosome 6)• Encode ionotropic glutamate receptorsEncode ionotropic glutamate receptors

Association of GRIK4 With Outcome of Association of GRIK4 With Outcome of AntidepressantAntidepressantTreatment in the STAR*D CohortTreatment in the STAR*D Cohort

• Am J Psychiatry 2007; 164:1181–1188Am J Psychiatry 2007; 164:1181–1188

• homozygote carriers of both the homozygote carriers of both the GRIK4 (11)GRIK4 (11)

• and HTR2A (13) genes were 23% less and HTR2A (13) genes were 23% less likely to experience nonresponse to likely to experience nonresponse to treatment relative to participants treatment relative to participants who did not carry any of these who did not carry any of these marker allelesmarker alleles

Serotonin Receptor 2A Gene and the InfluenceSerotonin Receptor 2A Gene and the Influenceof Childhood Maternal Nurturance on of Childhood Maternal Nurturance on AdulthoodAdulthoodDepressive SymptomsDepressive Symptoms

• Arch Gen Psychiatry. 2007;64:356-360Arch Gen Psychiatry. 2007;64:356-360

• Individuals carrying the Individuals carrying the TT//T T or or TT//C C genotype of the T102C polymorphism of genotype of the T102C polymorphism of the the HTR2A HTR2A gene (13) were responsive to gene (13) were responsive to the protective aspects of nurturing the protective aspects of nurturing mothering, so that in the presence of mothering, so that in the presence of high maternal nurturance, they high maternal nurturance, they expressed low levels of depressive expressed low levels of depressive symptoms, while this was not true with symptoms, while this was not true with the carriers of the the carriers of the CC//C C genotype.genotype.

Natural Hx and risk factorsNatural Hx and risk factors

Prediction From Low Birth WeightPrediction From Low Birth Weightto Female Adolescent Depressionto Female Adolescent Depression

• Arch Gen Psychiatry. 2007;64:338-344Arch Gen Psychiatry. 2007;64:338-344• 1420 participants1420 participants• 49% were female49% were female• prevalence of depression among prevalence of depression among

adolescent girls with LBW was 38.1% adolescent girls with LBW was 38.1% compared with compared with

• 8.4% among adolescent girls with normal 8.4% among adolescent girls with normal birth weightbirth weight

• No difference with no adversitiesNo difference with no adversities

Arch Gen Psychiatry. 2007;64:338-344Arch Gen Psychiatry. 2007;64:338-344

Association of Different Adverse Life Association of Different Adverse Life EventsEventsWith Distinct Patterns of Depressive With Distinct Patterns of Depressive SymptomsSymptoms

• Am J Psychiatry 2007; 164:1521–Am J Psychiatry 2007; 164:1521–15291529

• 4,856 individuals4,856 individuals

• (53% female) (53% female)

• who experienced depressive who experienced depressive symptoms in the previous year were symptoms in the previous year were assessedassessed

Am J Psychiatry 2007; 164:1521–1529Am J Psychiatry 2007; 164:1521–1529

Families at High and Low Families at High and Low Risk for DepressionRisk for Depression• Arch Gen Psychiatry. 2005;62:29-36Arch Gen Psychiatry. 2005;62:29-36

• Longitudinal, retrospective cohort, family study.Longitudinal, retrospective cohort, family study.• 161 grandchildren and their parents and grandparents161 grandchildren and their parents and grandparents

• major findings of this 3-generation study are major findings of this 3-generation study are • the moderating effects of grandparental depression on the moderating effects of grandparental depression on

the association between parental depression and the association between parental depression and grandchild diagnosesgrandchild diagnoses

• the importance of impairment in depression criteria the importance of impairment in depression criteria • the finding that anxiety disorders are an early sign of the finding that anxiety disorders are an early sign of

psychopathology in children from depressed familiespsychopathology in children from depressed families

Effect of Age at Onset on the Effect of Age at Onset on the CourseCourseof Major Depressive Disorderof Major Depressive DisorderAm J Psychiatry 2007; 164:1539–1546Am J Psychiatry 2007; 164:1539–1546• the older age-at-onset groups, especially the late-the older age-at-onset groups, especially the late-

adult-onset group, had the mildest, least pervasive, adult-onset group, had the mildest, least pervasive, least dysfunctional, and less recurrent formsleast dysfunctional, and less recurrent forms

• Earlier ages of onset were associated with Earlier ages of onset were associated with substantial functional impairment (e.g., poor social substantial functional impairment (e.g., poor social and occupational function, poor quality of life) and occupational function, poor quality of life)

• and greater illness burden (more current general and greater illness burden (more current general medical and psychiatric comorbidity, medical and psychiatric comorbidity,

• a more negative view of life and the self, a more negative view of life and the self, • more lifetime episodes of depression, more lifetime episodes of depression, • more severe depressive episodes, more severe depressive episodes, • more lifetime suicide attempts, more lifetime suicide attempts, • and greater suicidal ideation)and greater suicidal ideation)

Effect of Age at Onset on the Effect of Age at Onset on the CourseCourseof Major Depressive Disorderof Major Depressive DisorderAm J Psychiatry 2007; 164:1539–1546Am J Psychiatry 2007; 164:1539–1546

Prevalence and Distribution of Major Prevalence and Distribution of Major DepressiveDepressiveDisorder in African Americans, Caribbean Disorder in African Americans, Caribbean Blacks,Blacks,and Non-Hispanic Whitesand Non-Hispanic Whites

• Arch Gen Psychiatry. 2007;64:305-Arch Gen Psychiatry. 2007;64:305-315315

• 3570 African Americans, 3570 African Americans,

• 1621 Caribbean blacks, and 1621 Caribbean blacks, and

• 891 non-Hispanic whites 891 non-Hispanic whites

• aged 18 years and older (N=6082)aged 18 years and older (N=6082)

Arch Gen Psychiatry. 2007;64:305-315Arch Gen Psychiatry. 2007;64:305-315

• Lifetime MDD prevalence estimates were highest for Lifetime MDD prevalence estimates were highest for whites (17.9%), followed by Caribbean blacks (12.9%) whites (17.9%), followed by Caribbean blacks (12.9%) and African Americans (10.4%) and African Americans (10.4%)

• 12-month MDD estimates across groups were similar12-month MDD estimates across groups were similar• The chronicity of MDD was higher for both black The chronicity of MDD was higher for both black

groups (56.5% for African Americans and 56.0% for groups (56.5% for African Americans and 56.0% for Caribbean blacks) than for whites (38.6%). Caribbean blacks) than for whites (38.6%).

• Fewer than half of the African Americans (45.0%) and Fewer than half of the African Americans (45.0%) and fewer than a quarter (24.3%) of the Caribbean blacks fewer than a quarter (24.3%) of the Caribbean blacks who met the criteria received any form of MDD who met the criteria received any form of MDD therapy.therapy.

• In addition, relative to whites, both black groups were In addition, relative to whites, both black groups were more likely to rate their MDD as severe or very severe more likely to rate their MDD as severe or very severe and more disabling.and more disabling.

A Longitudinal Study of the Use of Mental Health A Longitudinal Study of the Use of Mental Health ServicesServicesby Persons With Serious Mental Illness: Do Spanish-by Persons With Serious Mental Illness: Do Spanish-SpeakingSpeakingLatinos Differ From English-Speaking Latinos and Latinos Differ From English-Speaking Latinos and Caucasians? Caucasians? Am J Psychiatry 2007; 164:1173–1180Am J Psychiatry 2007; 164:1173–1180

A Qualitative Analysis of the Perception of A Qualitative Analysis of the Perception of Stigma Among Latinos Receiving Stigma Among Latinos Receiving Antidepressants Antidepressants Psychiatric Services Psychiatric Services 58:1591–1594, 58:1591–1594, 20072007

• Antidepressant use was seen as implying more Antidepressant use was seen as implying more severe illness, weakness or failure to cope with severe illness, weakness or failure to cope with problems, and being under the effects of a problems, and being under the effects of a drugdrug

• Stigma was a prominent concern among Stigma was a prominent concern among Latinos receiving antidepressants, and Latinos receiving antidepressants, and

• stigma often affected adherence. stigma often affected adherence.

• culture is likely to play an important role in the culture is likely to play an important role in the communication of stigma and its associated communication of stigma and its associated complicationscomplications

Does Stigma Keep Poor Young ImmigrantDoes Stigma Keep Poor Young Immigrantand U.S.-Born Black and Latina Womenand U.S.-Born Black and Latina WomenFrom Seeking Mental Health Care? From Seeking Mental Health Care? Psychiatric Services Psychiatric Services 58:1547–1554, 200758:1547–1554, 2007

Changes in Health Care Use and CostsChanges in Health Care Use and CostsAfter a Break in Medicaid CoverageAfter a Break in Medicaid CoverageAmong Persons With Depression Among Persons With Depression Psychiatric Services Psychiatric Services 58:49–54, 200758:49–54, 2007

• Utilization of emergency and inpatient services and Utilization of emergency and inpatient services and Medicaid expenditures significantly increased for Medicaid expenditures significantly increased for beneficiaries with depression when they returned to beneficiaries with depression when they returned to Medicaid after experiencing a temporary loss in Medicaid after experiencing a temporary loss in coverage, coverage,

• especially for beneficiaries with a documented disability.especially for beneficiaries with a documented disability.• significant increases in the utilization of inpatient and significant increases in the utilization of inpatient and

emergency services are experienced by enrollees when emergency services are experienced by enrollees when returning to Medicaid after an interruption in coveragereturning to Medicaid after an interruption in coverage

• suggesting that some individuals may be reenrolled in suggesting that some individuals may be reenrolled in Medicaid by providers when presenting for acute care Medicaid by providers when presenting for acute care services. services.

• The causes for the observed increased utilization of The causes for the observed increased utilization of acute care services are not known.acute care services are not known.

The Costs and Benefits of The Costs and Benefits of Enhanced Depression Care to Enhanced Depression Care to Employers Employers

Arch Gen Psychiatry. 2006;63:1345-1353Arch Gen Psychiatry. 2006;63:1345-1353 • Hypothetical cohort of 40-year-old workers. Hypothetical cohort of 40-year-old workers. • Our societal perspective analyses suggest that a Our societal perspective analyses suggest that a

program of enhanced depression care for workers, program of enhanced depression care for workers, consisting of a 1-time workplace depression screen plus consisting of a 1-time workplace depression screen plus telephonic care management for depressed employees, telephonic care management for depressed employees, yields gains in quality-adjusted life expectancy at a cost yields gains in quality-adjusted life expectancy at a cost in the range seen for commonly accepted medical in the range seen for commonly accepted medical interventions covered by employer-sponsored health interventions covered by employer-sponsored health plans plans

• These results suggest that, like primary care depression These results suggest that, like primary care depression interventions, enhanced depression care for workers interventions, enhanced depression care for workers appears to be a good investment of society’s resources. appears to be a good investment of society’s resources.

FDA advisoryFDA advisory

Effects on treatmentEffects on treatment

Decline in Treatment of Pediatric Depression After Decline in Treatment of Pediatric Depression After FDAFDAAdvisory on Risk of Suicidality With SSRIs Advisory on Risk of Suicidality With SSRIs Am J Psychiatry 2007; 164:884–891Am J Psychiatry 2007; 164:884–891

Decline in Treatment of Pediatric Depression After Decline in Treatment of Pediatric Depression After FDAFDAAdvisory on Risk of Suicidality With SSRIs Advisory on Risk of Suicidality With SSRIs Am J Psychiatry 2007; 164:884–891Am J Psychiatry 2007; 164:884–891

• Pediatricians and nonpediatrician primary care Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions physicians accounted for the largest reductions in new diagnoses. in new diagnoses.

• Among patients with depression, the proportion Among patients with depression, the proportion receiving no antidepressant increased to three receiving no antidepressant increased to three times the rate predicted by the preadvisory times the rate predicted by the preadvisory trend trend

• SSRI prescription fills were 58% lower than SSRI prescription fills were 58% lower than predicted by the trend. predicted by the trend.

• There was no evidence of a significant increase There was no evidence of a significant increase in use of treatment alternatives (psychotherapy, in use of treatment alternatives (psychotherapy, atypical antipsychotics, and anxiolytics).atypical antipsychotics, and anxiolytics).

Spillover Effects on Treatment of Adult Spillover Effects on Treatment of Adult DepressionDepressionin Primary Care After FDA Advisory on Risk ofin Primary Care After FDA Advisory on Risk ofPediatric Suicidality With SSRIsPediatric Suicidality With SSRIsAm J Psychiatry 2007; 164:1198–1205Am J Psychiatry 2007; 164:1198–1205

Spillover Effects on Treatment of Adult Spillover Effects on Treatment of Adult DepressionDepressionin Primary Care After FDA Advisory on Risk ofin Primary Care After FDA Advisory on Risk ofPediatric Suicidality With SSRIsPediatric Suicidality With SSRIsAm J Psychiatry 2007; 164:1198–1205Am J Psychiatry 2007; 164:1198–1205

• The October 2003 advisory was the first in a The October 2003 advisory was the first in a series of risk communications series of risk communications

• a second public health advisory followed in a second public health advisory followed in October 2004 October 2004

• February 2005 black box warning and February 2005 black box warning and language for a patient medication guide were language for a patient medication guide were implemented which was nonspecific and implemented which was nonspecific and stated that youths and adults may be at riskstated that youths and adults may be at risk

• May 2007- the FDA extended the black box May 2007- the FDA extended the black box warning to include young adults, ages 19–24warning to include young adults, ages 19–24

Frequency of Provider Contact After FDA Frequency of Provider Contact After FDA Advisory on Risk of Pediatric Suicidality With Advisory on Risk of Pediatric Suicidality With SSRIsSSRIsAm J Psychiatry Morrato et al.; AiA:1–9Am J Psychiatry Morrato et al.; AiA:1–9

• The medication guide provides information for The medication guide provides information for parents, including a frequency schedule suggesting parents, including a frequency schedule suggesting that pediatric patients should have a total of seven that pediatric patients should have a total of seven visits with their physician during the first 3 months of visits with their physician during the first 3 months of antidepressant drug therapy—once a week for the antidepressant drug therapy—once a week for the first month, every 2 weeks for the second month, and first month, every 2 weeks for the second month, and a visit at 3 months.a visit at 3 months.

• Between the initial advisory and the black box Between the initial advisory and the black box warning, the FDA also issued a public health advisory warning, the FDA also issued a public health advisory about use of antidepressants in adults and about use of antidepressants in adults and strengthened warnings about the need to monitor all strengthened warnings about the need to monitor all patients for worsening of depression, especially early patients for worsening of depression, especially early in treatment and after dosage changesin treatment and after dosage changes


• Less than 5% of all patients met FDA Less than 5% of all patients met FDA contact recommendations before the contact recommendations before the advisoryadvisory

• and the rate did not change after the and the rate did not change after the advisory.advisory.

Intervention StudiesIntervention Studies

Drugs and MoreDrugs and More

Early Onset of Selective SerotoninEarly Onset of Selective SerotoninReuptake Inhibitor Antidepressant ActionReuptake Inhibitor Antidepressant ActionArch Gen Psychiatry. 2006;63:1217-1223Arch Gen Psychiatry. 2006;63:1217-1223

• Randomized controlled trials of SSRIs vs placebo Randomized controlled trials of SSRIs vs placebo for the treatment of unipolar depression in adults for the treatment of unipolar depression in adults that reported outcomes for at least 2 time points that reported outcomes for at least 2 time points in the first 4 weeks of treatmentin the first 4 weeks of treatment

• Treatment with SSRIs rather than placebo was Treatment with SSRIs rather than placebo was associated with clinical improvement by the end associated with clinical improvement by the end of the first week of the first week

• A secondary analysis indicated an increased A secondary analysis indicated an increased chance of achieving a 50% reduction in Hamilton chance of achieving a 50% reduction in Hamilton Depression Rating Scale scores by 1 week Depression Rating Scale scores by 1 week (relative risk, 1.64; 95% confidence interval, 1.2-(relative risk, 1.64; 95% confidence interval, 1.2-2.25) with SSRI treatment compared with placebo. 2.25) with SSRI treatment compared with placebo.

• Treatment with SSRIs is associated with Treatment with SSRIs is associated with symptomatic improvement in depression by the symptomatic improvement in depression by the end of the first week of use, and the improvement end of the first week of use, and the improvement continues at a decreasing rate for at least 6 continues at a decreasing rate for at least 6 weeks.weeks.

Combined Treatment With SertralineCombined Treatment With Sertralineand Liothyronine in Major Depressionand Liothyronine in Major DepressionArch Gen Psychiatry. 2007;64:679-688Arch Gen Psychiatry. 2007;64:679-688

• Response = 70% sertraline-liothyronine Response = 70% sertraline-liothyronine • 50% sertraline-placebo (50% sertraline-placebo (PP=.02; odds ratio, 2.93; 95% =.02; odds ratio, 2.93; 95%

confidence interval, 1.23-7.35); confidence interval, 1.23-7.35); • remission rates were 58% with sertraline-liothyronineremission rates were 58% with sertraline-liothyronine• and 38% with sertraline-placebo and 38% with sertraline-placebo • ((PP=.02; odds ratio, 2.69; 95% confidence interval, 1.16-=.02; odds ratio, 2.69; 95% confidence interval, 1.16-

6.49). 6.49). • Baseline T3 values were lower in patients treated with Baseline T3 values were lower in patients treated with

sertralineliothyronine who had remissions than in those sertralineliothyronine who had remissions than in those without remissions (without remissions (tt48=3.36; 48=3.36; PP.002)..002).

• Among patients treated with sertraline-liothyronine, Among patients treated with sertraline-liothyronine, remission was associated with a significant decrease in remission was associated with a significant decrease in serum thyrotropin values (F1,73=4.00; serum thyrotropin values (F1,73=4.00; PP.05). .05).

• There were no significant effects of liothyronine There were no significant effects of liothyronine supplementation on frequency of adverse effects.supplementation on frequency of adverse effects.

A Comparison of Lithium and T3 A Comparison of Lithium and T3 AugmentationAugmentationFollowing Two Failed Medication TreatmentsFollowing Two Failed Medication Treatmentsfor Depression: A STAR*D Reportfor Depression: A STAR*D ReportAm J Psychiatry 2006; 163:1519–1530Am J Psychiatry 2006; 163:1519–1530

• 142 adult outpatients with nonpsychotic major 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved depressive disorder who had not achieved remission or who were intolerant to an initial remission or who were intolerant to an initial prospective treatment with citalopram and a prospective treatment with citalopram and a second switch or augmentation trialsecond switch or augmentation trial

• Remission rates with lithium and T3 Remission rates with lithium and T3 augmentation for participants who augmentation for participants who experienced unsatisfactory results with two experienced unsatisfactory results with two prior medication treatments were modest and prior medication treatments were modest and did not differ significantly. 16% vs.25%did not differ significantly. 16% vs.25%

Cognitive Reactivity to Sad Mood Cognitive Reactivity to Sad Mood ProvocationProvocationand the Prediction of Depressive and the Prediction of Depressive RelapseRelapseArch Gen Psychiatry. 2006;63:749-755Arch Gen Psychiatry. 2006;63:749-755• In phase 1 of this study, patients with major depressive In phase 1 of this study, patients with major depressive

disorder were randomly assigned to receive either disorder were randomly assigned to receive either antidepressant medication or cognitive behavior antidepressant medication or cognitive behavior therapy.therapy.

• In phase 2, patients who achieved clinical remission In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then underwent sad mood provocation and were then observed with regular clinical assessments for 18 observed with regular clinical assessments for 18 monthsmonths

• Patients who recovered through antidepressant Patients who recovered through antidepressant medication showed greater cognitive reactivity medication showed greater cognitive reactivity following the mood provocation than those who following the mood provocation than those who received cognitive behavior therapy. received cognitive behavior therapy.

• Regardless of type of prior treatment, the magnitude of Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months.predictor of relapse over the subsequent 18 months.

Controlled Trial of Naturalistic Dawn Simulation Controlled Trial of Naturalistic Dawn Simulation andandNegative Air Ionization for Seasonal Affective Negative Air Ionization for Seasonal Affective DisorderDisorderAm J Psychiatry 2006; 163:2126–2133Am J Psychiatry 2006; 163:2126–2133

Controlled Trial of Naturalistic Dawn Controlled Trial of Naturalistic Dawn Simulation andSimulation andNegative Air Ionization for Seasonal Affective Negative Air Ionization for Seasonal Affective DisorderDisorderAm J Psychiatry 2006; 163:2126–2133Am J Psychiatry 2006; 163:2126–2133• Posttreatment improvement results were Posttreatment improvement results were • bright light, 57.1%; bright light, 57.1%; • dawn simulation, 49.5%; dawn simulation, 49.5%; • dawn pulse, 42.7%; dawn pulse, 42.7%; • highdensity ions, 47.9%; highdensity ions, 47.9%; • and low-density ions, 22.7% (significantly lower). and low-density ions, 22.7% (significantly lower). • Contrary to the authors’ hypothesis, analysis of Contrary to the authors’ hypothesis, analysis of

variance failed to find superiority of dawn variance failed to find superiority of dawn simulation to the dawn pulse or bright light. simulation to the dawn pulse or bright light.

• However, the dawn pulse led to a pattern of However, the dawn pulse led to a pattern of residual or exacerbated depressive symptoms residual or exacerbated depressive symptoms similar to those seen in low-density ion similar to those seen in low-density ion nonrespondersnonresponders

PosttestPosttest