Contraception and I have no disclosures to report depression - PowerPoint PPT Presentation

10/18/2017 Disclosures Contraception and • I have no disclosures to report depression Jennifer Kerns , MD, MS, MPH Associate Professor UCSF, Division of ZSFG October 18, 2017 What do depression and What is the percentage of US women 15-44 yrs contraceptive use have in common? old who currently use some form of contraception? Stigma A. 35% 52% B. 50% C. 62% Contraception Female Depression D. 79% 20% 16% 13% High prevalence % % % % 5 0 2 9 3 5 6 7 1

10/18/2017 Prevalence of any contraceptive use, What methods of contraception are most 2011-2013 commonly used to least commonly used among women in the US? A. Pill… female sterilization… male 43% 42% condom B. Male condom… pill… IUDs and implants C. Female sterilization… male condom… pill 8% 6% D. IUDs and implants… pill… male condom Male condom… pill… IUD... Female sterilization… ma.. Pill… female sterilization... IUDs and implants… pill... CDC/NCHS 2011-2013 Who is most likely to use which Method mix method? Pill … -higher education -older age -white Female sterilization… -lower education -older age -Hispanic -non-Hispanic black IUDs and implants… -Hispanic >white>black -25-34 age group 2

10/18/2017 Epidemiology of major Depression: diagnosis and depressive disorder natural history POINT PREVALENCE in US • Untreated depression  8% • Lifetime prevalence (10 countries)  5 symptoms 6% • Poorer quality of life  present most of the day ~ 3% to 17% 4%  nearly every day • Increased risk of suicide 2%  at least 2 weeks • Poorer outcomes when co- • Annual prevalence rate US 6.7% 0% • Depressed mood* occurring w/ medical conditions 1991/1992 2001/2002 • Loss of interest or pleasure in most • Lifetime prevalence rate US 16.5% or all activities* • Few patients discuss depressive • Insomnia or hypersomnia • Women (2x as high as men) RISK FACTORS • Change in appetite or weight symptoms – more often present  • Psychomotor retardation or agitation Prior depressive episode • Younger adults • Low energy  w/ somatic symptoms Family history • Poor concentration  Female gender • Thoughts of worthlessness or guilt • Frequently undetected in the absence  Childbirth • Estimated 50% of patients w/ • Recurrent thoughts about death or  Childhood trauma of screening suicide major depression are identified  Stressful life events • ~ 10% to 47% of cases undetected  Poor social support  Serious medical illness DMS-5, Major Depression  Andrade et al. Int J Methods Psychiatr Res 2003 Dementia Tylee and Gandhi. Prim Care Companion J Clin Psychiatry 2005 Kessler et al. Arch Gen Psychiatry 2005 Simon et al. NEJM 1999  Substance abuse Pignone et al. Ann Intern Med 2002 Mitchell et al. Lancet 2009 Etiology of depression Hormones and depression • Over-production of corticotropin releasing hormone  excess activity of HPA axis • Higher concentration of inflammatory markers • Abnormal functioning of neurotransmitters (serotonin, norepi, dopamine, GABA, glutamate) • Estrogen modulates serotonergic function • Progestins with low androgenicity may be more favorable with mood symptoms Joffe et al. Biol Psychiatry 1998 Schaffir et al. Eur J Contraception Reprod Health Care 2016 Wittenborn et al. Psychological Medicine 2015 3

10/18/2017 Which types of studies yield the Depression in pregnancy highest level of evidence? (choose the best answer) • Prevalence of unipolar depression in pregnancy is 7% (12% including major or minor) A. Systematic reviews & meta-analyses 56% • Genetic susceptibility, hormonal changes, B. Prospective cohort studies using large psychological and social factors registry-based database studies C. Meta-analyses & randomized controlled • Risk factors include unintended or unwanted 17% trials (RCTs) pregnancy 11% 9% 7% D. Prospective observational studies & RCTs • Associated w/ adverse pregnancy and neonatal E. All studies with a control group . . . . . . . . . . . e . i . m a . outcomes d o l m n u o o r t d t & s i n n t t a a o s r v c w o r r e a e h & o s h v i s b c t e e o i r e s w y e c v v i i a l s t t i e a c n t i e c d m p a e - u e s a p t t o t s s s e o Gregoriadis et al. J Clin Psychiatry 2013 r l y P M r l S P A Pearlstein. Best Pract Res Clin Obstet Gynaecol 2015 How can we assess causal Systematic review of CHC and association? depression Bradford Hill criteria • Included studies w/ estrogen-progestin method • Strength (effect size) • Studies had to measure mood, affect, or diagnosis of • Consistency (reproducibility) depression • Specificity • Very few RCTs or prospective studies • Temporality • Biological gradient • Heterogeneity of mood measurement and HC formulations • Plausibility • Coherence • Experiment Standardized screening tools Ethinyl estradiol dose Self-report Progestin type and dose • Analogy Interview Consistency of dose (mono vs triphasic) Mood changes, non standardized Administration (transdermal, oral, vaginal) Hill et al. Proc R Soc Med 1965 Schaffir et al. Eur J Contraception Reprod Health Care 2016 4

10/18/2017 Dose and dose consistency – Studies of HC and depression do they matter? • 1 RCT: LNG-only pill vs. LNG/EE pill vs. placebo • Older studies (when EE doses were higher) reported a • Lowest incidence of depression in LNG-only group greater prevalence of depression • No difference in depression by 3 months across groups • Inconsistent results from more recent studies • 4 large retrospective observational studies (3 HC, 1 COC) • RCT of 20 vs 30 mcg EE  higher depr w/ lower dose • 3 showed no association between HC and depression • RCT of 25 vs 35 mcg EE (+ norgestimate), triphasic • 1 showed lower depression among HC users • No difference in depression • Improved premenstrual sx’s w/ 25 mcg pill • 7 other observational studies – no difference or HC is protective • Triphasic vs monophasic pills  more mood changes • 1 pilot study (n=58) showed higher depression scores among COC • Changing dose, not total progestin that matters users • Also fewer symptoms w/ continuous use Toffol et al. Hum Reprod 2011 Toffol et al. Contraception 2012 Oddens et al. Contraception 1999 Graham et al. Contraception 1995 Keyes et al. Am J Epidemiol 2013 Oinonen et al. J Psychosom Res 2001 Akerlund et al. Br J Obstet Gynaecol 1993 Warner et al. J Psychosom Res 1988 Duke et al. Contraception 2007 Svendal et al. J Affect Disord 2012 Berenson et al. AJOG 2008 Greco et al. Contraception 2007 Bancroft et al. J Psychosom Res 1993 Marriott et al. J Psychosom Res 1986 Natale et al. Biol Rhythm Res 2006 Almagor et al. J Psychosom Res 1991 Walker et al. Psychosom Med 1990 Kulkarni et al. Aust Fam Physician 2005 Does route of administration What about type of progestin? matter (pill, patch ring)? • RCT comparing desogestrel vs LNG pills • Vaginal ring vs COCs  fewer depressive symptoms • More positive affect changes w/ desogestrel • RCT of patch users vs desogestrel pill • Observational study of gestodene COC vs other COC • Patch associated with higher emotional well being • Switchers  improved depression & mood • Prospective observational study patch vs LNG pill (teens) • 2 RCTs of drospirenone COC vs LNG COC • No difference in mood • Improved mood and affect in drospirenone group • RCT of patch vs ring • Observational studies of drospirenone  improved mood • No difference in mood swings Shahnazi et al. Iran Red Crescent Med J 2014 Borenstein et al. J Reprod Med 2003 Deijen et al. Contraception 1992 Skrzypulec et al. Eur J Contracept Reprod Health Care 2008 Sabatini et al. Contraception 2006 Sucato et al. J Pediatric Adolesc Gynecol 2011 Kelly et al. Clin Drug Investig 2010 Zimmerman et al. Contraception 2015 Lopez et al. Cochrane Database Syst Rev 2013 Creinin et al. Obstet Gynecol 2008 Sangthawan et al. Contraception 2005 Urdl et al. Eur J Obstet Gynecol Reprod Biol 2005 5