Depression Therapeutics

What percentage of people with MDD will receive adequate treatment?

20%

What are the goals of treatment for MDD?

• achieve remission of depressive symptoms

• recover optimal functioning

• recover QoL

• prevent suicide 

• prevent recurrences 

• ensure patient safety and acceptance of treatments 

What are the 2 main phases of MDD treatment?

• getting a patient with MDD well (acute phase)

• keeping a patient with MDD well (maintenance phase)

What is the typical duration of the acute phase of MDD? 

~8-16w until symptom remission 

What are the main objectives during the acute phase of MDD?

• address patient safety 

  • suicide and safety risks

  • inpatient vs outpatient 

  • safety plan 

• treat to symptom remission and functional improvement 

  • use psychoeducation and self-management 

  • select and start treatment(s) 

  • monitor efficacy and safety 

What is considered remission in MDD and why are we aiming to achieve it?

• remission → resolution or near-resolution of symptoms

  • lowered risk of relapse if achieve remission 

  • failure to achieve associated with continued symptom burden and worse functional outcomes 

What is the typical duration of the maintenance phase of MDD?

~6-24months post-acute phase

• may be longer if clinically indicated → if many recurrent episodes may stay on indefinitely

What are the main objective during the maintenance phase of MDD?

• maintain symptomatic remission

  • adjust treatment(s) if needed

  • address residual symptoms

• restore function and QoL to baseline

  • use psychoeducation and self-management

  • treat comorbid conditions

  • consider additional psychosocial interventions

• prevent recurrence

  • psychoeducation to identify early symptoms so can have early intervention 

  • monitor long-term ADEs if continuing meds

  • address barriers

  • promote resilience

• consolidate gains during discontinuation

  • if clinically indicated

  • use proper tapering when stopping

What are the various non-pharm treatment options for MDD?

• psychoeducation

• lifestyle interventions

• psychotherapy 

• neuromodulation

• digital health interventions

What is psychoeducation?

• process of providing health teaching to people looking for or receiving mental health services

• aim is to dispel myths and stigma related to medications or role of stress

How can psychoeducation enhance medication adherence in MDD?

*shown to enhance adherence when certain themes discussed 

• take med daily 

• talk to someone if experiencing ADEs 

• may take 2-4 weeks to see any noticeable difference from antidepressant 

• continue taking even if feeling better

• suicidal ideation is NOT normal ADE that need to tolerate → talk to us, there are other options 

• do not stop taking before checking; withdrawal 

What are the different lifestyle interventions with evidence in MDD and how can they help

*can decrease risk of developing MDD and severity of symptoms of MDD

• exercise

• sleep 

• smoking

• light therapy 

• diet 

What is the evidence for exercise as a lifestyle non-pharm intervention in MDD? 

• Highest level of evidence for lifestyle non-pharm (med-large benefit) 

  • can reduce suicidal thoughts 

  • better than nothing

  • better than standard treatment monotherapy

• Monotherapy or adjunctive 

  • mild → monotherapy okay

  • moderate → adjunctive 

What are the specific recommendations for exercise that show benefit in MDD?

• supervised low to moderate intensity exercise

• 30-40 minutes 

• 2-4x/week (work up to) → min 9 weeks 

• age specific benefits seen with: 

  • adolescents/youth → moderate/high aerobic intensity 

  • adults → HIIT

  • midlife/older females → low/mod intensity

What is the evidence for sleep as a lifestyle non-pharm intervention in MDD? 

• bidirectional

  • poor sleep quality/quantity can increase risk of MDE

  • MDD patients often have insomnia/hypersomnia

  • insomnia/poor sleep often remains after other MDD symptoms resolved

• some evidence shows evidence that improving sleep can help symptom improvement of MDD

  • 2nd line → adjunctive sleep hygiene and CBT-I 

  • 3rd line → adjunctive sleep deprivation 

What is the evidence for smoking cessation as a lifestyle non-pharm intervention in MDD? 

• bidirectional

  • people may smoke to cope with MDD symptoms (self-medicate) 

  • smoking increases vulnerability to depression 

What is the evidence for light therapy as a lifestyle non-pharm intervention in MDD? 

• helps maintain healthy circadian rhythms 

• first-line for SAD - MDEs with seasonal (winter) pattern

• second line for

  • mild nonseasonal MDE

  • adjunctive moderate MDE

What is the specific recommendation for light therapy non-pharm intervention?

1000, lux white light for 30 minutes daily (soon after waking)

What is the evidence for diet as a lifestyle non-pharm intervention in MDD? 

• not great evidence

  • observational studies → Western diet > severity and prevalence 

  • interventional (small) → modest benefit with Mediterranean diet

• 3rd line → adjunctive healthy diet or Mediterranean diet

What is psychotherapy?

• “talk" therapy

• different techniques that aim to help patients identify emotions, thoughts and behaviours that may be troublesome

  • first-line: CBT, IPT, BA

  • second-line: CBASP, mindful-CBT, PST, STPP

  • third-line: ACT, PDT, MCT, MI

• performed by licensed professional 

  • 1:1 or group settings 

What needs to be considered before recommending psychotherapy to a patient with MDD?

• efficacy of type of psychotherapy 

  • shown benefit in the acute phase

• severity of MDD

  • determines urgency, not the type of psychotherapy

• availability and patient preference 

• no mixed models 

  • each session must be completely 1 type, can add but not bits and pieces 

• if any history of suicide attempt

  • CBT specifically shown to reduce suicide attempts by 50% in patients that previously attempted (highest rates if attempt was in last 6 months)

*pt demographics do NOT affect choice of psychotherapy

What is the recommendation for psychotherapy for mild MDD with low safety risk?

• psychotherapy equally effective as pharmacotherapy

  • consider psychotherapy as first-line treatment (preferably CBT, IPT or BA) as has a lower risk profile

*only if readily available

What is the recommendation for psychotherapy for moderate MDD with low/mod safety risk?

• psychotherapy equally effective as pharmacotherapy

  • short-term → pharm > improvement core depressive symptoms

  • long-term → CBT more efficacious

• combo psychotherapy + pharm MORE effective than either as monotherapy

  • consider combination therapy of psychotherapy and pharmacotherapy as it leads to better outcomes than either monotherapy

What is the recommendation for psychotherapy for severe MDD with high safety risk without psychosis?

• combo psychotherapy + pharm MORE effective than either as monotherapy

  • can start at same time or sequentially 

What is the recommendation for psychotherapy for severe MDD with high safety risk with psychosis?

• pharmacotherapy more effective than psychotherapy

  • need to start antidepressant + antipsychotic 

  • psychotherapy DOES NOT treat psychosis 

• psychotherapy can be deferred and started once psychosis resolved 

What is neurostimulation?

• treatments that alter CNS activity through the use of electrical or magnetic stimulation of the brain

  • electroconvulsive therapy (ECT) 

  • transcranial magnetic stimulation (rTMS) 

When is neurostimulation used in MDD? 

• typically reserved for when primary (1st and 2nd line) options have not completed remission

• ECT

  • 1st line if severe MDE where experiencing severe features of psychosis, catatonia, suicidal ideation or deteriorating physical condition in acute and maintenance phase 

  • 2nd line in DTD in acute phase 

• rTMS

  • 1st line for TRD in acute phase

What is the efficacy of neurostimulation?

• response rate 65-75% in depressive episodes

  • higher efficacy in → older adults,+  psychosis or catatonia

• relapse risk of 60-80% recurrence within 6 months post-treatment 

  • recommend continued pharmacotherapy or maintenance ECT to sustain remission 

What is the typical treatment course of neurostimulation?

• ~6-12 sessions

  • occurring 2-3x/week

What are the contraindications for ECT? 

• recent MI, occurred < 8 weeks ago 

• increased intracranial pressure 

• recent cerebral hemorrhage 

• loose teeth (full dental exam b/c can dislodge and be choking hazard) 

• retinal detachment 

• using MAOI 

• caution: 

  • medications that increase the seizure threshold → b/c goal is to create a “low-grade” seizure

What are digital health interventions?

• when patient uses technology (computers, phones, wearables) for purpose of screening, monitoring, treatment and prevention of recurrence

What is the evidence for digital health interventions as a non-pharm intervention in MDD? 

• potential iCBT (digital CBT) for first-line mild MDD

• potential for adjunct first-line in moderate MDD

What are the pros and cons to digital health interventions?

• pros 

  • convenient and real-time feedback (esp if access to psychotherapy an issue)  

  • shown to have some benefit in mild/mod MDD 

• cons

  • privacy issues 

  • compliance issues → only 1/3 patients continue after 6 weeks 

  • not fully evaluated for efficacy and safety 

What is the evidence for antidepressants as a pharm intervention in MDD? 

• all antidepressants have confirmed efficacy versus placebo

If all antidepressants better than placebo, how do we decide to choose one? 

• choosing antidepressant based on: 

  • efficacy (for specific symptoms)

  • adverse effect profile 

  • cost 

  • patient preference 

  • previous history → inefficacy of one, does not mean will fail another either in same class or different class 

What is tachyphylaxis regarding with antidepressants?

• aka poop out

• where tolerance may occur due to possible CNS adaptations, worsening disease pathogenesis or incorrect diagnosis 

• if occurs at max dose → add adjunct if still partially effective, or switch to another antidepressant 

What are the different drug classes of antidepressants?

• SSRIs

• SNRIs

• TCAs

• NDRI

• MAOIs

• serotonin reuptake inhibitor/5-HT1A agonist 

• alpha-2 antagonist/5-HT2 antagonist 

• serotonin reuptake inhibitor/5-HT2 antagonist 

• serotonin reuptake inhibitor/5-HT1A/B agonist/5-HT1D/3A/7 antagonist 

What are the different SSRI antidepressants?

• citalopram

• escitalopram

• fluoxetine

• fluvoxamine

• paroxetine

• sertraline

What are the different SNRI antidepressants?

• venlafaxine

• desvenlafaxine

• duloxetine

• levomilnacipran 

What are the different TCA antidepressants?

• amitriptyline 

• desipramine

• imipramine

• nortriptyline 

• clomipramine 

• doxepin 

What are the different NDRI antidepressants?

• bupropion

What are the different MAOI antidepressants?

• phenelzine

• tranylcypromine

• moclobemide 

What are the different serotonin reuptake inhibitor/5-HT1A agonist antidepressants?

• vilazodone

What are the different alpha-2 antagonist/5-HT2 antagonist antidepressants?

• mirtazapine

What are the different serotonin reuptake inhibitor/5-HT2 antagonist antidepressants?

• trazodone 

What are the different serotonin reuptake inhibitor/5-HT1A/B agonist/5-HT1D/3A/7 antagonist antidepressants?

• vortioxetine