STRATEGIES FOR TREATING DEPRESSION FOR PEOPLE LIVING WITH HIV - - PowerPoint PPT Presentation

Conall O’Cleirigh, P.h.D The Fenway Institute Massachusetts General Hospital Harvard Medical School Boston, MA

STRATEGIES FOR TREATING DEPRESSION FOR PEOPLE LIVING WITH HIV

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DEPRESSIO N IS HIG HL Y PREVA L ENT IN PA T IENT S W IT H HIV

• Rates of depression among persons with HIV

infection range from 20-37% in epidemiological and sample studies

(O’Cleirigh et al., 2014; Atkinson & Grant, 1994; Bing et al., 2001; Cruess et al., 2003)

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DEPRESSIO N A ND A DHERENC E

• Depressed patients are 3 times greater than non-

depressed patients to be non-adherent to medical treatment recommendations

• Depressive symptoms are correlated with worse

ART adherence, detectable viral load, and accelerated disease progression

• Patients with depression are more likely to miss

appointments with their HIV physician

(Gonzalez, et al., 2011; Wagner et al., 2011; Dimatteo et al., 2000; Safren et al., 2001, Catz et al., 2000, Patterson et al., 2000; Holzemer et al., 1999)

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ST RESSO RS REL A T ED T O L IVING W IT H HIV

• Living with a chronic medical condition
• Opportunistic infections
• Maintaining health and medication adherence
• Economic stress
• Employment / disability
• Child care
• Confidentiality
• Comorbidities

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SIG NIFIC A NC E O F T REA T ING DEPRESSIO N IN HIV

• Depression may moderate the ability of a patient to

benefit from health-behavior interventions that do not address depression

• Efforts to address symptoms of depression may

improve adherence to HIV medications, thus:

• Improving virologic outcomes
• Reducing HIV-related morbidity and mortality rates
• Implications for HIV transmission
• HIV adherence and engagement in care interventions

for individuals with mental health disorders are lacking

(Amico et al., 2006; Simoni et al., 2006)

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C BT FO R A DHERENC E A ND DEPRESSIO N (C BT

• A D) IN HIV
• Psychoeducation/Motivational

Interviewing about CBT for Depression (1 session)

• Behavioral Activation/Activity
• Scheduling (1 session)
• Adaptive Thinking (5 sessions)
• Problem Solving (2 sessions)
• Relaxation/Diaphragmatic

Breathing (2 sessions)

Each session builds on the previous session and each session integrates adherence skills.

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FIRST ST UDY R2 1 INT EG RA T ING T HE T REA T M ENT O F DEPRESSIO N W IT H A DHERENC E C O UNSELING IN HIV

• 2 Arm, cross-over design comparing

12 sessions of CBT-AD to a single session of adherence counseling

• Participants: 45 randomized, 42

completers with DSM-IV diagnosable depression

• CBT-AD resulted in improved

adherence (MEMS=pill cap) and depression at 3 months, and gains were maintained at 6 and 12 months.

• Those who “crossed over” caught up

after completing the full intervention

Safren SA, O’Cleirigh CO, Tan JY, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009;28:1-10. MEMS Adherence outcomes

25 50 75 100 BASELINE T2 CBT ETAU

F(1,42) = 21.94, p< .0001, Effect size (Cohen d) = 1.0

HAM-D outcomes 5 10 15 20 25

BASE T2

F(1,42) = 6.32, p < .02, Cohen d = .82

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LESSO NS LEA RNED - FLEX IBILIT Y IN DELIVERING T HE INT ERVENT IO N (DELIVERED BY DO C T O RA L O R M A ST ERS LEVEL PSYC HO LO G IST S)

• Therapist adherence – to general principals of

CBT and the manual versus every session following the outline

• Flexibility of adapting the modules
• Flexibility in sequence of modules
• Flexibility in time spent on modules
• Bring current problems back to CBT skills for

adherence and depression

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T A RG ET (SEC O ND ST UDY): C BT FO R M EDIC A T IO N A DHERENC E A ND DEPRESSIO N IN HIV+ IDU

• 2 arm study (ETAU or CBT-AD) NIDA R01
• Participants (N=89) recruited from substance use treatment

clinics and community in Massachusetts and Rhode Island

• History (or current) IDU but in SU treatment

Safren, O’Cleirigh, et al., 2012 – JCCP.

• 62% at least one additional DSM-IV

diagnosis

• 42% two or more additional DSM-IV

diagnoses

• Panic d/o 30%
• GAD 18%
• Social anxiety d/o 14%
• PTSD 10%

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C BT FO R A DHERENC E A ND DEPRESSIO N IN HIV- INFEC T ED IDU (N= 8 9 ): A C UT E O UT C O M ES

• MEMs-based Adherence: HLM

analysis of MEMs Weeks 0-10 = greater improvement in treatment versus control condition (slope = 0.887, t(86)= 2.38, p = .02)

65 70 75 80 85 M E M S Adherence (% ) P ast W eek

15 17 19 21 23 25 27 29 31 Pre Randomization Post Treatment Control CBT-AD

• Depression: Pre-Post Treatment:

Significantly greater improvements in depression in treatment versus control condition [MADRS (F(1,79)=6.52, p<.01)] (replicated with clinical global impression [(F(1,79)=14.77, p<.001)] )

Safren, O’Cleirigh et al., 2012 – JCCP

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CBT-AD/ETAU ART Adherence (MEMS) Depression

Support for Integrated Treatment Model

(γslope =0.48, t(86) = 1.35, p=.18) (γslope=0.717, t(87) = 2.01, p<.05)

(γslope = 0.032, t (86) = 1.98, p =.05)

(F(1, 79 = 6.52, p <.01).

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O UT C O M ES A FT ER INT ERVENT IO N DISC O NT INUA T IO N (6 A ND 1 2 M O NT HS)

• Depression: gains were maintained
• MEMS-based adherence: somewhat attenuated
• Viral load: No differences across conditions
• CD4: the CBT-AD condition had significant improvements in

CD4 cell counts over time compared to ETAU (γslope= 2.09, t (76) = 2.20, p = .03)

• 61.2 CD4 cell increase intervention condition
• 22.4 CD4 cell decrease control condition

Safren et al., 2012 – JCCP

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LESSO NS LEA RNED

• Depression treatment integrated into substance

use treatment can be effective

• Flexibility to work in the context of multiple co-
• ccurring mental health problems
• Utility of harm reduction approach for ongoing or

substance use relapse

• Bring current problems back to CBT skills for

adherence and depression

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T REAT MENT MANUAL

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T RIA D (T HIRD ST UDY): M ET HO D

• CBT for Medication Adherence and Depression in HI V+ Patients
• Participants recruited from HIV treatment clinics and community in

Massachusetts and Rhode Island

• Randomized to CBT-AD, ISP-AD, or ETAU
• Stratified by current or prior problem with injection drug use, prescribed

medications for the treatment of their depression, and study site

• I nclusion Criteria:
• HIV-positive
• Have been prescribed ART for at least 2

months

• Have either a current diagnosis of

depression or be prescribed an anti- depressant medication for a depression diagnosis and have at least some residual depressive symptoms (having met full clinical criteria prior to antidepressant initiation).

• 18 years of age or older

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• 3 arm study (2:2:1 randomization)
• Life-Steps plus provider letter
• CBT-AD
• Information/supportive

psychotherapy

• Large N (240; 80 randomized per

site)

• 217 (90%) completers
• 3 site study (MGH, Brown, Fenway)
• Wide inclusion criteria
• Incremental cost effectiveness

analysis

STUDY DESIGN

NIMH funded efficacy trial (PI: Safren) R01MH084757-05 NIMH R-01 MH084757

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PARTICIPANTS

N = 2 4 0 Age M ( SD) 4 7 .4 ( 8 .4 ) Gender n ( % ) Male 1 6 5 ( 6 8 .7 ) Fem ale 7 5 ( 3 1 .3 ) African Am erican/ Black 6 8 Caucasian/ W hite 1 5 6 Other 3 1 Hispanic/ Latino n ( % ) Yes 2 6 ( 1 0 .8 ) No 2 1 4 ( 8 9 .2 ) Education n ( % ) Partial high school or less 3 3 ( 1 3 .8 ) High school graduate 6 5 ( 2 7 .1 ) Partial college 7 0 ( 2 9 .2 ) College graduate 7 2 ( 3 0 .0 ) On Disability n ( % ) Yes 1 3 9 ( 5 7 .9 ) No 1 0 1 ( 4 2 .1 ) Sexual Orientation n ( % ) Gay/ bisexual 1 3 6 ( 5 6 .9 )

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DURING T HE T REA T M ENT PERIO D, C BT

• A D

A C HIEVED SIG NIFIC A NT LY IM PRO VED M EM S A ND C ESD SC O RES C O M PA RED T O ET A U

• Com pared to ETAU, CBT-AD

dem onstrated:

• A significant increase in

adherence over the treatment period (Est.=1.00, 95% CI=0.34, 1.66, p=0.003).

• Significantly greater

improvement in self-reported depression scores over the treatment period (Est.=-0.41, 95% CI=-0.66, -0.16, p=0.001).

MEMS-based adherence and depression (CESD) scores are adjusted through mixed-effects analyses.

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A T PO ST T REA T M ENT , C BT

• A D HA D

SIG NIFIC A NT LY LO W ER DEPRESSIO N RA T ING S C O M PA RED T O ET A U

CBT-AD ETAU Significance level CGI 2.60 (0.13) 3.26 (0.18) 0.005 MADRS 17.65 (1.03) 22.33 (1.38) 0.007

Data are mean (SE). Scores are adjusted for baseline outcome measures and through the use of ANCOVA.

• Month 4 (when controlling baseline):
• CGI (Est.=-0.66, 95% CI=-1.11,-0.21, p=0.005)
• MADRS (Est.=-4.69, 95% CI=-8.09,-1.28,

p=0.007)

Safren, Bedoya, O’Cleirigh, et al In Press Lancet HIV

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DURING FO LLO W - UP, SIG NIFIC A NT G A INS IN A DHERENC E, SELF- REPO RT ED DEPRESSIO N, A ND C G I- A SSESSED DEPRESSIO N W ERE M A INT A INED FO R T HE C BT

• A D A RM C O M PA RED T

O T HE ET A U A RM

• The gains acquired for the CBT-AD arm compared to the ETAU arm over

follow-up in:

• Adherence, m aintained (Est.=-4.54, 95% CI=-9.71, 0.62,

p=0.09).

• Self-reported depression, maintained(Est.=0.88, 95% CI=-0.66,

2.43, p=0.26).

• CGI -assessed depression, maintained (Est.=0.18, 95% CI= -

0.10, 0.42, p=0.24).

• MADRS-assessed depression, maintained (Est.=-2.06, 95% CI=-

4.96, 0.83, p=.16) and these changes were not different by condition (Est.=1.32, 95% CI= -0.54, 3.17, p=0.16).

Month 4 Month 8 Month 1 2

CBT-AD ETAU CBT-AD ETAU CBT-AD ETAU MEMS 81.66 (2.39) 69.76 (3.17) 75.61 (2.22) 68.25 (2.96) 69.55 (3.04) 66.73 (4.07) CESD 20.75 (0.86) 25.04 (1.16) 21.41 (0.76) 24.81 (1.04) 22.07 (0.94) 24.59 (1.27) CGI 2.62 (0.13) 3.15 (0.18) 2.67 (0.11) 3.05 (0.15) 2.72 (0.14) 2.94 (0.19) MADRS 17.90 (1.02) 21.16 (1.37) 17.84 (0.88) 19.78 (1.19) 17.78 (1.07) 18.40 (1.46)

Data are mean (SE). Scores are adjusted for baseline outcome measures and through the use of mixed-effects analyses

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T HERE W ERE NO SIG NIFIC A NT DIFFERENC ES BET W EEN C BT

• A D, ISP- A D, A ND ET

A U O N VIRA L LO A D O R C D4 C ELL C O UNT

• CBT-AD vs ETAU at post treatm ent:
• Controlling for baseline, there were no significant differences in log viral load

(Est.=-0.11, 95% CI=-0.31,0.09, p=0.288) or CD4 cell count (Est.=-8.69, 95% CI=-73.31,55.92, p=0.791) between CBT-AD and ETAU at month 4.

• CBT-AD vs ETAU over follow -up:
• There were no significant differences for log viral load (Est.=-0.05, 95%

CI=-0.18, 0.07, p=.41) or CD4 cell count (Est.=-44.10, 95% CI= -96.93, 8.72, p=0.10) between CBT-AD and ETAU over follow-up.

• CBT-AD vs I SP-AD at post treatm ent:
• After controlling for baseline values, there were no significant differences in

log viral load (Est.=-0.11, 95% CI=-0.27,0.06, p=0.211) or CD4 cell count (Est.=-9.69, 95% CI=-69.16,49.78, p=0.748) between CBT-AD and ISP-AD at month 4.

• CBT-AD vs I SP-AD over follow -up:
• There were no significant differences for log viral load (Est.=0.02, 95% CI=
• 0.09, 0.12, p=0.78) or CD4 cell count Est.=5.12, 95% CI=-32.14, 42.37,

p=0.79) between CBT-AD and ISP-AD over follow-up.

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CBT‐AD development: Conception, pilot, efficacy, and effectiveness

1. Co nc e ptio n a nd pilo t (CF AR de ve lo pme ntal award, S afre n) 2. Ra ndo mize d pilo t tria l - pa tie nts in HI V c a re (R21 MH066660, S afre n) 3. E ffic a c y study in PL WHA with inje c tio n drug use histo rie s (R01 DA018603, S afre n) 4. E xte nsio n to type 2 dia b e te s (R01 MH078571, S afre n) 5. Hyb rid e ffic a c y/ e ffe c tive ne ss e ffic a c y study in pa tie nts in HI V c a re (R-01 MH084757, S afre n) 6. E xte nsio n to multiple comorbidities (K24K24MH094214, Safren) 7. E ffe c tive ne ss a nd imple me nta tio n

 Spanish translation on U.S. Mexico Border (5R34MH084674, Simoni)  S. Afric a with nurse inte rve ntio nists (pilo t c o mple te , NI

H R01 pro po sa l pe nding , S afre n, O’ Cle irig h, Jo ska)

 Zimb a b we Pro je c t with Adhe re nc e Co unse lo rs: Pilo t RCT  T

e le me dic ine w/ Afric a n Ame ric a n wo me n in de e p so uth (R34MH097588, Ke mpf)

 We b b a se d ve rsio n (Co o k/ He rsc h S BI R, 5RC1DA028505)

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T HA NK YO U

• Collaborators:
• Dr. Steve Safren
• Dr. Kenneth Mayer
• Dr. Roger Weiss
• Dr. Deb Herman
• Dr. Nafisseh Soroudi
• Dr. Robert Malow
• Dr. Christina Psaros
• Dr. Andres Bedoya
• Dr. John Joska
• Dr. Lena Andersen
• Dr. Melanie Abas
• Dr. Jonathan Lerner
• Dr. Jeffrey Gonzalez
• Dr. Joseph Greer
• Dr. Robert Knauz
• Norma Reppucci
• Joan Cremins
• Susan Adams
• Betty Bredin
• Cal Dyer
• Research Coordinators
• Jessica Coleman
• Giselle Perez
• Susie Michelson
• Pamela Handelsman
• Luis Serpa
• Laura Reilly
• Jared Israel
• Jackie Bullis
• The Participants!
• The Hospitals:
• Massachusetts General Hospital
• Fenw ay Health
• The Miriam Hospital
• Cape Tow n Research Team
• University of Miam i
• King’s College Research Team
• Harare Research Team

NI MH Funding: R01MH084757-05 Clinical Trial Registration: Therapy Targeting Depression and HIV Treatment Adherence (NCT00951028; https: / / clinicaltrials.gov/ ct2/ show/ NCT00951028).

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ZIMPHAMANDL A: A ST UDY AIMED AT ADAPT ING A C O G NIT IVE- BEHAVIO RAL BASED INT ERVENT IO N FO R ADHERENC E AND DEPRESSIO N IN HIV T O T HE SO UT H AFRIC AN C O NT EXT

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G O A LS A ND RESEA RC H T RA JEC T O RY

• To develop a culturally-

appropriate, short-term, cost-effective treatment for depression

• Treatment must be highly

structured and manualized

• Needs to be administered

by primary care staff

• Feasibility, acceptability

and effectiveness need to be ascertained

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A DA PT ED C BT

• A D PRO T

O C O L (ZIM PHA M A NDLA )

• The intervention comprises 6-8 sessions of nurse-

administered CBT-AD lasting 1 hour each

• The session modules are as follows:
• Module 1 – Life Steps for HIV Medication
• Module 2 – Psychoeducation / MI
• Module 3 – Activity Scheduling
• Module 4 – Problem-solving
• Module 5 – Relaxation and Diaphragmatic

Breathing

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C ES- D RESULT S

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HA M - D PRE- A ND PO ST

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SHEEHA N PRE- A ND PO ST

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C URRENT R0 1 EFFIC A C Y/ EFFEC T IVENESS T RIA L ZIM PHA M A NDLA

• The intervention comprises 7 sessions of CBT-AD lasting 1

hour each integrated into HIV Primary Care

• Intervention delivered by Nurses
• Participants (n = 1600: Living with HIV from Cape Town

townships who have failed first line treatment.

• Incremental cost effectiveness compared to enhanced

treatment as usual.

• The session modules are as follows:
• Module 1 – Life Steps for HIV Medication
• Module 2 – Psychoeducation / MI
• Module 3 – Activity Scheduling
• Module 4 – Problem-solving
• Module 5 – Relaxation and Diaphragmatic Breathing

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T RA INING HIV A DHERENC E C O UNSEL O RS IN C O G NIT IVE BEHA VIO RA L T HERA PY FO R DEPRESSIO N: PREL IM INA RY W O RK IN HA RA RE, ZIM BA BW E A ND FUT URE W O RK

JESSICA F. MAGIDSON, PH.D. POSTDOCTORAL FELLOW BEHAVIORAL MEDICINE CHESTER M. PIERCE, MD DIVISION OF GLOBAL PSYCHIATRY

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2- DA Y C LINIC A L T RA INING W ho?

• 3 adherence counselors
• Supervising psychologists

W hat?

• Life-Steps, CBT approaches

for depression (behavioral activation, problem solving)

How ?

• Didactics, role play, feedback

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KEY C HA LLENG ES

• Kufungisisa
• Translates as “thinking too much”
• ‘Cultural concept of distress’ in DSM-5
• Is this really ‘depression’?
• Training general CBT skills to counselors
• Interpretation of words in Shona
• (“why did you not take your HIV pills?”)

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PLA N

• Select and adapt adherence intervention
• Integrate with depression intervention
• Pilot the integrated intervention

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T HE INT ERVENT IO N: NEW DIREC T IO N (“NZIRA IT SVA ”)

• Adapted Life-Steps, evidenced-based cognitive

behavioral intervention (CBI) to improve ART adherence

• (Safren et al 2001, Safren, O’Cleirigh, et al 2009).
• Adapted for local Zimbabwean adult population
• (Bere et al Journal of Health Psychology, 2016)
• Checklist of barriers :
• Getting to clinic (financial constraints),
• Talking to doctor,
• Coping with side effects,
• Forgetting

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O UT C O M ES

• Electronically measured adherence in past 2

weeks =>90%

• Depression using Patient Health Questionnaire
• Fidelity to intervention
• Viral suppression <200 copies/ml
• Appointment adherence

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SO M E PRELIM INA RY RESULT S

• High uptake, session attendance, and follow-up at 6

months

• 32 enrolled: 14 Intervention Arm, 18 Control Arm
• Mean age 35,
• 67% female,
• 40% U/E,
• 28% primary school only,
• 81% on first line ART,
• 97% viral non-suppression at baseline
• Preferences for PST-AD over usual care

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KEY DIFFERENC ES FRO M US BA SED W O RK

• Language
• Greater number of sessions
• Use of an educational video
• Cadre of the Adherence Counselors
• Culturally-competent probes
• Integrated with stepped care for

depression based on problem-solving therapy (not CBT)

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T HA NK YO U!

JESSICA F. MAGIDSON, PH.D. POSTDOCTORAL FELLOW BEHAVIORAL MEDICINE CHESTER M. PIERCE, MD DIVISION OF GLOBAL PSYCHIATRY