Depression Special Populations

What is the perinatal period?

The period of time when you become pregnant and up to a year after giving birth. 

What is the prevalence of depression in the perinatal period?

• at any point has prevalence up to 12.5%

• postpartum depression highest risk within first 6 months

  • 1/5 serious depressive symptoms

  • 1/14 experience MDE

What are the risk factors for MDE during the perinatal period?

• psychiatric/psychological

  • history PMADs (perinatal mood & anxiety disorder) or other mood/anxiety disorder untreated before/during pregnancy

  • history premenstrual dysphoric disorder

  • prior trauma

  • perfectionistic or anxious personality traits

• social/lifestyle 

  • low social support

  • domestic conflict/intimate partner violence 

  • isolation (recent immigration)

  • financial insecurity/unemployment/housing instability

• physical/obstetric

  • prior peripartum complications (unplanned pregnancy, miscarriage) 

  • hormonal sensitivities 

• demographics/sociocultural 

  • adolescence

  • racialized or Indigenous 

  • gender and sexual minorities 

What should be included in the perinatal assessment? 

• early detection is important 

• should use standardized tools → Edinburgh Postnatal Depression Scale 

• trauma-informed care 

What are the non-pharm treatment options in management of PMADs?

• psychotherapy

• lifestyle interventions

  • exercise

  • nutrition 

  • sleep

What is the evidence for psychotherapy in PMADs?

• effective in preventing 

  • especially if there is a history of depression, mild depressive symptoms or risk factors for PMADs 

• effective in treating MDE during perinatal period ± co-occurring anxiety 

• first-line → CBT & IPT 

  • can be provided by non-specialist providers (nurses, midwives)

  • particularly for anxiety/fear of childbirth

• second-line → guided self-help (prevention for risk of mild symptoms)

What is the recommendation for starting psychotherapy in perinatal period?

• CBT 4-16 weekly sessions

• one day CBT workshops

  • beneficial for postpartum depression and anxiety

• in-person or virtual and group or individual all efficacious 

What is the evidence for exercise in PMADs?

• Can improve mood and reduce activity 

  • helping prevent symptoms

  • and may treat symptoms 

What is the recommendation for exercise in perinatal period?

• regular physical activity encouraged 

  • low/moderate 

  • under supervision to ensure clinically appropriate

• eg: walking, yoga and swimming

What is the evidence and recommendation for diet in PMADs and the perinatal period? 

• balanced diet rich in omega-3 and vitamins/minerals can support mental health 

• may refer to nutritional counseling to ensure adequate intake 

What is the evidence of sleep hygiene in PMADs?

• good sleep practices essential for managing mood and anxiety 

• sleep disruption is a known risk factor for all PMADs 

  • and is very common in perinatal period 

What are the recommendations for sleep hygiene during the perinatal period? 

• sleep protection 

  • highly recommended in patients with past history or active PMADs 

• maintain regular sleep schedule 

• create restful sleep environment 

• CBT-I 

What is the general safety of medications used in PMADs during pregnancy and lactation? 

• common psychotropic agents low risk in terms of:

  • pregnancy/postpartum outcomes (some exceptions)

  • lactation (infant dose < 10% = minimal risk; can use >10% in some cases) → extra caution in preterm or health issues

• data from large observations studies → bias and some uncertainty remains due to no RCTs 

Is there a risk of pregnancy complications with antidepressants?

• No clinical significance in: 

  • risk of spontaneous abortion 

  • gestational diabetes or HTN

• slight increase in postpartum hemorrhages with serotonergic agents

  • increase in blood loss NOT linked to more severe outcomes  

Is there a risk of congenital malformations with antidepressants?

• no increase with SSRIs, SNRIs or TCAs 

• small risk CV malformations w/ first trimester exposure SSRIs, SNRIs or bupropion 

  • paroxetine > risk vs other SSRIs 

• avoid MAOIs → case reports 

Is there a risk of neonatal complications with antidepressants?

• no impact fetal growth

• VERY rare PPHN (persistent pulmonary HTN of newborn)

  • most typically recover in 1-2 weeks with intervention

• 1/3 newborns exposed to SSRIs/SNRIs in pregnancy display transient symptoms of PNAS (poor neonatal adjustment syndrome) 

  • jitteriness, respiratory distress or irritability 

  • self-limited to 2-3d with supportive care

  • highest risk with → paroxetine, venlafaxine and fluoxetine

Is there a risk of long-term child health with antidepressants?

• no consistent relationship b/w any physical m neurodevelopmental or psychiatric problems

  • observed associations likely due to genetics and  environmental factors related to parental mental illness not medications themselves 

What are the fist-line recommended antidepressants used in pregnancy?

• due to safety, tolerability and efficacy

  • citalopram 

  • escitalopram 

  • sertraline 

What are the second-line recommended antidepressants used in pregnancy?

• bupropion → less safety data, case reports infant seizures w/ lactation

• desvenlafaxine → less safety data

• duloxetine → uncertainty w/ spontaneous abortion

• fluvoxamine → possibly higher PPHN and PNAS, longer half-life if breastfeeding

• mirtazapine → less safety data, uncertainty w/ spontaneous abortion 

• venlafaxine → possibly higher PNAS

What are the third-line recommended antidepressants used in pregnancy?

• paroxetine → possible higher risk CV malformations and PNAS

  • requires level 2 ultrasonography if was on prior to pregnancy and continuing 

• quetiapine → maternal and fetal metabolic impacts, sedation

• trazodone → maternal tolerability concerns

• TCAs → maternal tolerability concerns 

What are the antidepressants that should be avoided in pregnancy?

• ketamine

• MAOIs 

• newer ones (no data) → vilazodone, vortioxetine 

What is the general safety for second generation antipsychotics in pregnancy?

*may be used as adjunctive therapy 

• limited info on long-acting injectables 

• dose adjustments may be needed due to increased metabolism in pregnancy 

Is there a risk of pregnancy complications with antipsychotics?

• 2nd gen increased risk of metabolic effects like gestational diabetes

  • highest with olanzapine and quetiapine

• no increase in spontaneous abortion w/ 1st or 2nd gens

Is there a risk of congenital malformations with antipsychotics?

• no increased risk for major congenital malformations

• possible small risk CV malformations w/ risperidone use first-trimester 

• ziprasidone and lurasidone favourable safety profile 

Is there a risk of neonatal complications with antipsychotics?

• no increased risk of preterm or still birth 

• 2nd gen may have association with large for gestational age infants 

  • mixed data on small for gestational age infants

• some may have PNAS (typically mild and confounded with other factors)

Is there a risk of long-term child health complications with antipsychotics?

• possible transient delays in motor development

  • resolves in first 2 years 

• no increase in developmental, behavioural or cognition 

What are the recommendations for antidepressants during lactation?

• same as “during pregnancy”

• doxepin not recommended due to infant somnolence/sedation 

• avoid newer agents b/c lack of safety data 

*for non-breastfeeding postpartum individuals can follow standard MDD treatment guidelines

Is there a risk of pregnancy complications with lithium (may be used as adjunct)?

• not associated with spontaneous abortion, pre-eclampsia or postpartum hemorrhage

Is there a risk of congenital malformations with lithium (may be used as adjunct)?

• associated with cardiac malformation (Epstein’s anomaly) in first trimester 

  • malformation of tricuspid valve 

  • risk is dose-dependent 

  • absolute risk low 

• no major congenial malformations identified 

Is there a risk of neonatal complications with lithium (may be used as adjunct)?

• no risk of preterm birth

• elevated risk of:

  • hypoglycemia

  • thyroid abnormalities

  • nephrogenic diabetes insipidus (tubules not respond to antidiuretic hormone (ADH) →  excessive dilute urine and dehydration)

  • hypotonia (decreased muscle tone) 

  • 28d readmission to special care 

• no low birth weight increase 

• some data for increase risk of large for gestational age at birth 

Is there a risk of long-term child health complications with lithium (may be used as adjunct)?

• none identified 

What is the initiation process for acute agitation during pregnancy?

• use least restrictive option, then escalate as needed

  • verbal de-escalation → oral med → IM → physical restraint 

What are the recommended pharm options for acute agitation in pregnancy? 

• first-line → short acting benzodiazepine (lorazepam)) 

  • monotherapy preferred 

  • combo with antipsychotics if agitation also related to psychosis 

What are the preferred antipsychotics if need to use adjunct for acute agitation in pregnancy?

• olanzapine → safe and fast acting dissolve tabs or IM

• quetiapine → safe but slower onset 

• haloperidol → min risk and fast acting (IM) 

• loxapine → reasonable, but less data vs haloperidol 

Should monotherapy or combo therapy be used for PMADs?

• monotherapy recommended

  • combo may be associated with increased risk of adverse pregnancy/infant outcomes 

  • may need combo for bipolar, OCD and severe MDD; use classes with most safety data 

• do NOT lower dose to reduce exposure at expense of disease decompensation (risk of other issues)

How to help discussion about congenital malformation risk with psychoactive agents?

• inform them background congenital risk 3-5% 

  • can happen on meds or not 

  • absolute risk increase low if there is one 

What is the evidence to discuss when weight risk benefit of treating or not treating patient’s PMADs?

• untreated PMADs increase pregnancy/infant outcomes, including: 

  • early delivery 

  • low birth weight

  • delayed physical growth in early childhood 

• chronic stress may impact brain development in child 

• untreated PMADs can impair mother-infant bond (a crucial aspect of child’s emotional and social development) 

• worsening PMADs can lead to chronic mental illness and suicide 

• postpartum depression associated with:

  • lower rates of breastfeeding

  • reduced mother-infant interactions

  • higher rates of child physical illness, hospitalizations, cognitive, emotional and behavioural problems 

What is the risk of discontinuing antidepressants during pregnancy?

• increases risk of relapse if high severity depression 

  • therefore exposes them to all the untreated risks 

What does the general treatment plan look like for PMADs?

1. Preconception and planning (goal = remission, prevent relapse, min risk fetus)

   • if possible stabilize patient prior to conception

   • inform patient risk vs benefit treatment at all phases

2. Psychosocial interventions 

   • food, housing, intimate partner violence supports provided early 

3. Assess and Treat

   • guided by severity, past response, patient preference

   • use validated scales

4. Monitoring and follow-up

   • Q1-3W if symptomatic

   • Q6-8W once in remission

What are the initial treatment recommendations for mild PMAD?

• lifestyle ± psychosocial ± CAM interventions 

  • or psychological interventions, if others not feasible or accessible 

*can manage in community and primary care 

What are the initial treatment recommendations for moderate PMAD?

• lifestyle ± psychosocial ± CAM interventions 

• psychological interventions

• or pharmacological or neuromodulation, if:

  • patient preference

  • lack of access to others

  • diagnosis of bipolar or psychosis

  • high-risk of worsening/relapse

*should be managed with primary and specialist care 

What are the initial treatment recommendations for severe PMAD?

• lifestyle ± psychosocial ± CAM interventions 

• psychological interventions

• pharmacological or neuromodulation

*should be managed with specialist care 

What is the association with physical illness, age and depression?

• increasing age → increases risk of physical illness → increases risk of depression 

  • CVD, chronic pain, diabetes, PD strongly associated with depression 

What is the prognosis of depression in older adults? 

• late life depression has worse prognosis, higher relapse and medical morbidity versus earlier onset of MDD 

  • partly due to frailty, self-neglect and immobility

  • biological age more relevant than chronological age

• 20% of suicides occur in older adults

How does treatment response compare in older adults for MDD?

• respond to antidepressants at similar rates ~51%

• poorer outcomes seen with physical illness, anxiety and reduced executive function 

Is there a difference in efficacy and safety with antidepressants in older adults?

• generally equi-efficacious

• older adults may be more sensitive to side effects profiles 

  • may require lower doses than general population 

  • SSRIs, SNRIs and newer agents typically first-line due to preferable profile 

  • other antidepressants see higher rates of stroke, seizure and mortality (however causality unknown) 

  • anticholinergic effects of TCAs may increase dementia risk, unknown if other antidepressants do 

What are risk factors for depression in older adults? 

• recently bereaved with unusual symptoms 

  • active suicidal ideation, guilt not related to deceased, psychomotor slowing, mood congruent delusions 

• prolonged bereavement (3-6 months after the loss)

• socially isolated 

• persistent complaints of memory difficulties 

• chronic disabling illness 

• recent major physical illness 

• persistent sleep difficulties 

• significant comatic concerns or recent onset anxiety 

• refusal to eat or neglect personal care 

• recurrent or prolonged hospitalization 

• diagnosis dementia, PD or stroke 

• recent placement in nursing/LTC home 

What are the 3 levels of prevention of depression in older adults?

• universal → general population

• selective → focus on groups at high risk of developing mental illness 

• indicated → individual early symptoms or biological markers but not yet meeting diagnostic criteria 

What are some interventions for preventing MDD in older adults?

*strong emphasis on prevention in this population

• group-based interventions → reduce loneliness and depressive symptoms 

  • primarily in LTC; reminiscence therapy, exercise, video conferences, gender based social groups 

• social “prescribing” → may alleviate mild-mod depression, isolation and loneliness

  • links patients to community-based, non-clinical supports offered by volunteer sector (social, emotional or practical needs)

• stepped-care → prevents onset in community dwelling adults

  • if subthreshold anxiety/depression, watchful wait + CBT with a referral to primary care if/when medication required

• physical activity → lowers future depression risk

What are non-pharm interventions for treatment of MDD in older adults?

• psychotherapy, for those that can participate (no severe cognitive impairment or psychosis)

• Exercise and mind-body interventions 

What are the recommendations for psychotherapy in older adults for treatment of MDD? 

• monotherapy or combo pharmacotherapy

• HCPs with geriatric care experience

• best evidence:

  • CBT - solo or group 

  • problem-solving therapy (PST) - if executive dysfunction 

  • BA

What are the recommendations for exercise in older adults for treatment of MDD? 

• Tai chi

• yoga

• mindfulness-based stress reduction

What is the major difference in pharmacotherapy for MDD in older adults?

• similar to younger adults, but consider lower doses and potential drug interactions

  • PK changes in elderly can increase risk of accumulation 

What are the recommendations for mild MDD in older adults?

• if < 4 weeks → non-pharms

• if > 4 weeks and already tried psychotherapy → pharmacotherapy ± psychotherapy 

What are the recommendations for mild-mod MDD in older adults?

• pharmacotherapy ± psychotherapy 

What are the recommendations for severe MDD without psychosis in older adults?

• pharmacotherapy + psychotherapy

• ECT

  • especially if previously responded well

  • failed to respond to 1+ adequate antidepressant trials + psychotherapy 

What are the recommendations for severe MDD with psychosis in older adults?

• pharmacotherapy → antidepressant + antipsychotic 

• ECT if: 

  • failed response to combo meds after 4 weeks or poor tolerability 

  • symptoms severe enough to deem first-line (severe suicidality or health consequences) 

What special considerations need to be considered when selecting an antidepressant for older adults?

• anticholinergic effects → want lowest risk agents

• CV effects → want lower risk agents

What are the first-line recommendations for antidepressants in older adults? 

• duloxetine 

• sertraline

What are the second-line recommendations for antidepressants in older adults? 

• escitalopram

• citalopram (caution due to QTc prolongation)

What are the third-line recommendations for antidepressants in older adults? 

• TCAs → only when alternative not helpful, due to adverse side effects 

  • if need to be used nortriptyline and desipramine preferred due to lower incidence of anticholinergic burden

Which antidepressants should not be used in older adults, and why?

• fluoxetine → very long half-life (accumulation risk) 

• paroxetine → higher anticholinergic effect 

• MAOIs → high risk of drug-food and drug-drug interactions 

What does the follow-up look like for MDD in older adults? 

• Q1-2W to assess response and tolerability 

  • change or titrate dose if needed 

• 2-4W post initiation antidepressant 

  • serum sodium level assessed 

  • if incomplete response consider switch/augmentation 

What are potential augmentations for MDD in older adults? 

• another antidepressant

• lithium (caution due to renal toxicity)

• antipsychotics

• further specialized psycotherapy

When should treatment be assessed for discontinuation for MDD in older adults?

• continue at therapeutic dose for at least 1 year

  • slow tapper over several months if possible

• continue monitoring for recurrence of symptoms