Major Depressive Disorder (MDD) PDF

### Major Depressive Disorder +-----------------------------------+-----------------------------------+ | DSM-5 Criteria | | +===================================+===================================+ | A Criteria | - 5 or...

### Major Depressive Disorder +-----------------------------------+-----------------------------------+ | DSM-5 Criteria | | +===================================+===================================+ | A Criteria | - 5 or more symptoms in the | | | same 2 week period (occurring | | | nearly every day), with at | | | least 1 or either (1) or (2) | | | | | | 1. Depressed mood (NOTE: in | | | children and adolescents, can | | | be irritable mood) | | | | | | 2. Loss of interest or pleasure | | | | | | 3. Significant (ie. 5%) changes | | | to weight (+/-) or appetite | | | (NOTE: in children can be not | | | making expected weight gain) | | | | | | 4. Insomnia or hypersomnia | | | | | | 5. Psychomotor agitation or | | | retardation observable by | | | others | | | | | | 6. Fatigue or loss of energy | | | | | | 7. Worthlessness or guilt | | | | | | 8. Poor concentration or | | | indecisiveness | | | | | | 9. Recurrent suicidal ideation | | | or making a plan/attempt | +-----------------------------------+-----------------------------------+ | B Criteria | - Clinically significant | | | distress or impairment in | | | social, occupational, or | | | other areas of functioning | +-----------------------------------+-----------------------------------+ | Other Criteria | - Cannot diagnose with BAD or | | | schizoaffective | | | | | | - Can be diagnosed as | | | superimposed on other | | | psychotic disorders but if | | | not meet threshold for MDE, | | | likely describe depressive | | | symptoms as associated | | | feature | +-----------------------------------+-----------------------------------+ | Specifiers | | +-----------------------------------+-----------------------------------+ | [Severity/psychotic/remission | | | specifier ] | | | | | | - Mild/moderate/severe | | | | | | - With psychotic features | | | | | | - In partial or full remission | | | (2 month symptom free) | | | | | | - Unspecified | | | | | | [Episode Specifiers ] | | +-----------------------------------+-----------------------------------+ | With anxious distress | | +-----------------------------------+-----------------------------------+ | \*\*Associated with poorer | | | response to standard treatments, | | | higher suicide risk, and longer | | | duration of illness\*\* | | | | | | - Presence of 2+ during | | | majority of days: | | | | | | - Feeling keyed up or tense | | | | | | - Feeling unusually | | | restless | | | | | | - Difficulty concentrating | | | because of worry | | | | | | - Fear that something awful | | | might happen | | | | | | - Feel might lose control | | +-----------------------------------+-----------------------------------+ | With mixed features | | +-----------------------------------+-----------------------------------+ | \*\*Must monitor closely for | | | activating side effects or manic | | | switch | | | | | | \*\*Significant risk of | | | developing bipolar disorder | | | | | | A. Presence of 3+ during | | | majority of days: | | | | | | - Elevated, expansive mood | | | | | | - Inflated self-esteem or | | | grandiosity | | | | | | - More talkative than usual | | | or pressure to keep | | | talking | | | | | | - Flight of ideas | | | | | | - Increase in energy or | | | goal directed activity | | | | | | - Increased or excessive in | | | activities with painful | | | consequences | | | | | | - Decreased need for sleep | | | | | | B. Must be observable by others | | | and be change in behaviour | | | from baseline | | +-----------------------------------+-----------------------------------+ | With melancholic features | | +-----------------------------------+-----------------------------------+ | \*\*More common in elderly | | | | | | - 1 of the following present | | | during most severe period of | | | MDE: | | | | | | A. Loss of pleasure in all | | | activities | | | | | | B. Lack of reactivity to | | | pleasurable stimuli, even | | | temporarily | | | | | | - 3+ of the following: | | | | | | C. Distinct quality of | | | depressed mood with | | | profound despondency, | | | despair, moroseness, or | | | empty mood | | | | | | D. Worse in the morning | | | | | | E. Early morning awakening | | | | | | F. Psychomotor agitation or | | | retardation usually | | | present and observable | | | | | | G. Anorexia or weight loss | | | | | | H. ++Guilt | | +-----------------------------------+-----------------------------------+ | With atypical features | | +-----------------------------------+-----------------------------------+ | \*\*Women have this more common | | | | | | A. Mood reactive (ie. Brights to | | | positive events) | | | | | | B. 2+ of the following: | | | | | | - Weight gain or increase | | | in appetite | | | | | | - Hypersomnia (10+ hours | | | per day, or 2 hr increase | | | from baseline) | | | | | | - Leaden paralysis | | | | | | - Long standing pattern of | | | interpersonal rejection | | | sensitivity causing | | | impairment | | | | | | C. NOT melancholic or catatonic | | +-----------------------------------+-----------------------------------+ | With psychotic features | | +-----------------------------------+-----------------------------------+ | - Mood congruent: themes of | | | inadequacy, guilt, disease, | | | death, nihilism, or deserved | | | punishment | | | | | | - Mood incongruent | | +-----------------------------------+-----------------------------------+ | With catatonia | | +-----------------------------------+-----------------------------------+ | With peripartum onset | | +-----------------------------------+-----------------------------------+ | - Onset during pregnancy or | | | within 4 weeks of delivery | | +-----------------------------------+-----------------------------------+ | With seasonal pattern | | +-----------------------------------+-----------------------------------+ | - Regular temporal relationship | | | between MDE and season (ie. | | | Fall or winter) | | | | | | - Full remission at | | | characteristic time (ie. | | | Spring) | | | | | | - In last 2 years, two MDEs | | | with temporal relationship to | | | season and no MDE outside of | | | the season | | | | | | - Seasonal episodes outnumber | | | nonseasonal | | +-----------------------------------+-----------------------------------+ | Diagnostic Features | | +-----------------------------------+-----------------------------------+ | - Milder episodes, individuals | | | may report increased effort | | | to function or | | | insomnia/fatigue only | | | | | | - Anhedonia: lack of pleasure | | | | | | - Common somatic symptoms = | | | Neurovegetative symptoms | | | | | | - Fatigue, inattention, | | | insomnia & early morning | | | awakening, and poor | | | appetite | | +-----------------------------------+-----------------------------------+ | Mental Status Examination | | +-----------------------------------+-----------------------------------+ | - Mood: "depressed, sad, | | | hopeless, discourage, down in | | | the dumps" | | | | | | - Affect blunted or constricted | | | | | | - Behaviour | | | | | | - Increased irritability | | | | | | - Psychomotor retardation | | | | | | - Psychomotor agitation: | | | restless, pacing, | | | handwringing, rubbing | | | skin | | | | | | - Speech | | | | | | - Alogia (paucity of | | | unprompted speech) | | | | | | - Decrease in variety of | | | content | | | | | | - Thought content | | | | | | - Cotard's Syndrome: | | | walking corpse, | | | nihilistic delusion in | | | depression with | | | psychosis, believes that | | | nothing exists (ie. Body | | | parts, possessions, | | | organs) | | | | | | - Thought process | | | | | | - Rumination about loss, | | | guilt, suicide, and death | | | | | | - Cognition | | | | | | - Pseudodementia: in | | | elderly, chief complaint | | | may be about memory! | | +-----------------------------------+-----------------------------------+ | Etiology | | +-----------------------------------+-----------------------------------+ | Genetic | | +-----------------------------------+-----------------------------------+ | - Individuals with first degree | | | relative with MDD increased | | | odds ratio of 2.84 for | | | developing disease | | | | | | - Twin studies: heritability at | | | 37%, higher in woman | | +-----------------------------------+-----------------------------------+ | Epidemiology | | +-----------------------------------+-----------------------------------+ | - Worldwide: | | | | | | - 300 million worldwide | | | living with MDD in 2020 | | | | | | - Child: 3% of youth | | | worldwide have depressive | | | disorder | | | | | | - 20-30% of individuals | | | with MDE have chronic | | | depression lasting more | | | than 2 years | | | | | | - High mortality | | | | | | - Depression and | | | admitted to nursing | | | home = high | | | likelihood of death | | | in 1^st^ year | | | | | | - F \> M | | | | | | - Canada | | | | | | - Lifetime: 12% of | | | Canadians 12+ have a | | | lifetime episode of MDD | | | | | | - 1 year prevalence: 4.7% | | | of Canadians experienced | | | MDE in past year | | | | | | - United States | | | | | | - US Gender ratio: 2:1 F:M | | | | | | - US age ratio: age 18 to | | | 29 3x more prevalence | | | compared to 60+ | | +-----------------------------------+-----------------------------------+ | Risk and Prognostic Factors | | +-----------------------------------+-----------------------------------+ | Static, non-modifiable | - Female sex (abuse, | | | reproductive life stages) | | | | | | - Family history of mood | | | disorders (2 to 4x risk | | | compared to general | | | population) | | | | | | - ACEs | | | | | | - Death of spouse | | | | | | - Racialized, indigenous, | | | gender minority, religious | | | populations | +-----------------------------------+-----------------------------------+ | Dynamic | - Comorbid psychiatric or | | | medical illness | | | | | | - Temperament: neurotic | | | | | | - Substance use, esp. alcohol | | | | | | - Insomnia, night shift work | | | | | | - Hormonal changes (puberty, | | | pregnancy, menopause) | | | | | | - Stress | | | | | | - Bereavement | | | | | | - Bullying | | | | | | - Gender dysphoria | | | | | | - Sedentary lifestyle/screen | | | time | +-----------------------------------+-----------------------------------+ | Course of Illness | | +-----------------------------------+-----------------------------------+ | - Likelihood increases markedly | | | with puberty; 50% present | | | between ages 20 to 40 | | | | | | - Men more likely to engage in | | | maladaptive self-coping and | | | problem-solving (ie. | | | Substances, risk-taking) | | | | | | - Late-onset depression | | | associated with worse | | | prognosis, more chronic | | | course, higher relapse rate, | | | and higher levels of medical | | | comorbidity, cognitive | | | impairment, and mortality | | | | | | - Recovery for MDE with | | | antidepressant begins within | | | 3 months of onset for 40% and | | | within 1 year for 80% | | | | | | - Untreated episodes last 6 to | | | 13 months | | | | | | - Variable course, some never | | | experience remission, some | | | have discrete episodes | | | | | | - Considered a chronic | | | disorder, as disease | | | progresses, patients have | | | more frequent episodes | | | that last longer | | | | | | - Incidence of relapse | | | lower in those who | | | continue prophylactic | | | treatment | | | | | | Risk factors for: | | | | | | - Lower recovery rate | | | | | | - Psychosis | | | | | | - Prominent anxiety | | | | | | - Personality disorder | | | | | | - Severe illness | | | | | | - Lower risk of recurrence | | | | | | - Increased duration of | | | remission | | | | | | - Higher risk of recurrence | | | | | | - Persistence of mild | | | symptoms during remission | | | | | | - Multiple episodes | | | | | | - Bipolar conversion | | | | | | - More likely in onset of | | | depression in | | | adolescence, those with | | | psychosis, family history | | | of bipolar illness, and | | | mixed features | | | | | | - Postpartum depression | | | with psychotic features, | | | seasonality, hypomania | | | with antidepressants, | | | repeated loss of efficacy | | | of antidepressant after | | | initial response | | +-----------------------------------+-----------------------------------+ | Differential Diagnosis | | +-----------------------------------+-----------------------------------+ | Diagnosis | Differentiating Factors | +-----------------------------------+-----------------------------------+ | Any mood disorder | - Including adjustment, | | | schizoaffective, PMDD, PDD, | | | DMDD, substance-induced | +-----------------------------------+-----------------------------------+ | Another Medical condition | - Pharmacologic agents: steroid | | | contraceptives, | | | anticholinesterase | | | insecticides, amphetamine or | | | cocaine withdrawal, alcohol | | | or sedative withdrawal, | | | thallium, mercury | | | | | | - Endocrine-metabolic: hypo + | | | hyperthyroidism, | | | hyperparathyroidism, | | | hypopituitarism, Addison, | | | Cushing, DM | | | | | | - Infectious: toxoplasmosis, | | | influenza, viral hepatitis, | | | mono | | | | | | - Collagen: RA and lupus | | | erythematosus | | | | | | - Nutritional deficiency | | | | | | - Neurologic: Multiple | | | sclerosis, dementia, | | | Parkinson, head trauma, | | | complex partial seizures | | | (right temporal lobe | | | epilepsy), sleep apnea, | | | cerebral tumours, | | | cerebrovascular infarction | | | | | | - Neoplastic | +-----------------------------------+-----------------------------------+ | Bereavement | - Predominant affect is | | | emptiness and loss | | | | | | - Dysphoric mood decreases in | | | intensity over days to weeks | | | and occurs in waves | | | associated with reminders of | | | deceased | | | | | | - Emotional reactivity | | | preserved | +-----------------------------------+-----------------------------------+ | Co-morbidities | | +-----------------------------------+-----------------------------------+ | - 40 to 60% with anxiety | | | | | | - 10-30% for ADHD, SUD, | | | personality, and non | | | psychiatric illness (DM, CVD, | | | cancer, chronic pain) | | | | | | - High comorbidity with PTSD, | | | OCD, eating disorder | | | | | | - Female more like to report | | | comorbid anxiety, bulimia | | | nervosa, and somatoform | | | disorder | | | | | | - Men more likely to report | | | substance abuse | | | | | | - Comorbidity makes depression | | | harder to treat, still use | | | pharmacotherapy and | | | psychotherapy NOT less | | | effective with comorbid | | | personality | | +-----------------------------------+-----------------------------------+ | Investigations | | +-----------------------------------+-----------------------------------+ | - CBC and TSH, rule out anemia | | | and thyroid issues | | | | | | - ECG if hx of cardiovascular | | | disease or use of QTc | | | prolonging agents | | | | | | - Interleukin 8 and CRP | | | elevation correlated with | | | poor SSRI response, but | | | testing not recommended due | | | to small effect size | | | | | | - Neuroimaging if 1) | | | neurological signs, 2) sudden | | | change in mood/behaviour | | | etc, 3) cognitive | | | impairment, 4) late life | | | depression to rule out | | | cerebral event or structural | | | issue | | | | | | - Pharmacogenetic testing | | | | | | | | | | | | - Tests for variants in genes | | | that code for enzymes | | | responsible for metabolism, | | | some test variants in gene | | | coding for serotonin | | | transporter and receptors | | | | | | - High response and remission | | | rate, but modest effect size | | | | | | - Useful for those with severe | | | or unusual adverse effects or | | | poor response | | +-----------------------------------+-----------------------------------+ | Rating Scales | | +-----------------------------------+-----------------------------------+ | - Measurement-based care | | | improved medication adherence | | | and outcome, patient | | | engagement, high intervention | | | accuracy, shorter treatment | | | duration, and may identify | | | non-responders | | | | | | - Consider administer every 2 | | | to 4 weeks during acute | | | treatment, with reduction | | | during maintenance | | | | | | - Early improvement: | | | reduction in score by 20% | | | or greater within 2 to 4 | | | weeks of treatment | | | | | | - No early improvement | | | is strongly | | | associated with | | | non-response or | | | non-remission | | | | | | - Response: greater than | | | 50% improvement | | | | | | - Clinician-rated scales | | | | | | - Hamilton Depression | | | Rating Scale (HAM-D or | | | HAM-7) | | | | | | - Montgomery-Asberg | | | Depression Rating Scale | | | (MADRS) | | | | | | - Columbia Suicide Severity | | | Rating Scale (C-SSRS) | | | | | | - Patient-rated scales | | | | | | - Beck-Depression Inventory | | | II (BDI-II) | | | | | | - Patient Health | | | Questionnaire (PHQ-9) | | | | | | - Quick Inventory for | | | Depressive | | | Symptomatology, | | | self-rated (QIDS-SR) | | +-----------------------------------+-----------------------------------+ | Safety | | +-----------------------------------+-----------------------------------+ | - 5x higher than in general | | | population | | | | | | - Consider SADPERSONS scale | | | (Male **Sex, Age** 15 to 25 | | | or 59+ , **Depression, | | | Previous** attempt, | | | **Excessive** Drug use, | | | **Rational** thinking loss, | | | **single, organized** or | | | serious attempt, **No** | | | social support, **Stated** | | | future intent | | | | | | - US: likelihood of suicide | | | attempts less in middle and | | | late life, but risk of death | | | is same | | | | | | - Most deaths by suicide are | | | not preceded by non-fatal | | | attempts | | | | | | - Anhedonia most strongly | | | associated with suicidal | | | ideation | | | | | | - 4000 suicide deaths per year, | | | 50% have MDD | | | | | | | | | | | | - 15 deaths by suicide every | | | 100,000 males | | | | | | - 5 deaths by suicide every | | | 100,000 females | | +-----------------------------------+-----------------------------------+ | MODIFIABLE RISK FACTORS FOR | NON-MODIFIABLE RISK FACTORS FOR | | SUICIDE | SUICIDE | +-----------------------------------+-----------------------------------+ | - Symptoms and Life Events | - Older men | | | | | - SI with plan or intent | - Past attempts | | | | | - Hopelessness | - History of self-harm | | | | | - Anxiety | - Identifying as sexual | | | minority | | - Impulsivity | | | | - Family history of suicide | | - Psychosis | | | | - History of legal issues | | - Stress | | | | | | - Comorbid conditions | | | | | | - PTSD | | | | | | - SUD | | | | | | - Personality disorders | | | (esp. Cluster B) | | | | | | - Sleep disorders | | | | | | - Chronic pain | | +-----------------------------------+-----------------------------------+ | Treatments for Adults: CANMAT | | | 2023 | | +-----------------------------------+-----------------------------------+ | Treatment Algorithm | | +-----------------------------------+-----------------------------------+ | Note: COMBINATION of | | | psychotherapy and pharmacotherapy | | | is more effective than either | | | alone!!! | | | | | | Two phases of treatment: | | | | | | - Acute: 2 to 4 months, until | | | symptom remission (lowers | | | risk of relapse) | | | | | | - Maintenance: 6 to 24 months | | | or longer | | +-----------------------------------+-----------------------------------+ | ***MDE Severity*** | ***Summary Recommendations for | | | Initial Treatment*** | +-----------------------------------+-----------------------------------+ | Mild with low safety risk | Psychotherapy or Pharmacotherapy | | | (equally as effective, preference | | | for psychotherapy) | | | | | | Lifestyle interventions | | | | | | CAM | | | | | | Guided DHI | +-----------------------------------+-----------------------------------+ | Moderate, with low-moderate | Psychotherapy or Pharmacotherapy | | safety risk | OR BOTH (pharmacotherapy more | | | efficacious short-term and | | | psychotherapy more in | | | medium-term) | | | | | | Adjunct: lifestyle interventions, | | | CAM, and Guided DHI | +-----------------------------------+-----------------------------------+ | Severe, with moderate to high | Without psychosis: psychotherapy | | safety risk | and pharmacotherapy | | | | | | With psychosis: add antipsychotic | | | | | | Very severe/life threatening: | | | neuromodulation, such as ECT | +-----------------------------------+-----------------------------------+ | Biopsychosocial | | +-----------------------------------+-----------------------------------+ | Lifestyle interventions: | | | indicated as adjunct, for mild | | | severity MDE | | +-----------------------------------+-----------------------------------+ | First-line | 1. Supervised exercise (low to | | | moderate intensity, 30 to 40 | | | minutes, three to four times | | | a week for minimum 9 weeks) | | | for MILD severity. \*\*CAN | | | REDUCE SI\*\* | | | | | | 2. Light therapy (10,000 lux | | | white light for 30 minutes | | | daily) qAM for SEASONAL | | | pattern   | | | | | | \*monotherapy recommended for | | | seasonal depression  | +-----------------------------------+-----------------------------------+ | Second-line | 1. Light therapy for MILD, | | | NON-SEASONAL | | | | | | 2. Adjunctive exercise for | | | MODERATE severity | | | | | | 3. Adjunctive sleep hygiene and | | | CBT-insomnia | | | | | | 4. Adjunctive healthy diet (high | | | fruit, vegetables, fibre, and | | | low content of saturated fat | | | and carbohydrates) | +-----------------------------------+-----------------------------------+ | Third-line | 1. Adjunctive Mediterranean diet | | | | | | 2. Adjunctive sleep deprivation | | | (rapid, but transient effect) | +-----------------------------------+-----------------------------------+ | Complementary and Alternative | | | Medicine Treatments (none have | | | evidence comparable to | | | psychotherapy or pharmacotherapy) | | +-----------------------------------+-----------------------------------+ | First-line | St. John's Wart for MILD \*\*Risk | | | of serotonin syndrome and potent | | | CYP3A4 inhibitor\*\* | +-----------------------------------+-----------------------------------+ | Second-line | Acupuncture for MILD | | | | | | St. John's Wart for MODERATE | | | | | | Adjunct acupuncture for MODERATE | | | | | | Adjunctive L-methyl-folate for | | | MODERATE | +-----------------------------------+-----------------------------------+ | Third-line | Adjunctive S-adenosyl methionine | | | for MILD TO MODERATE | | | | | | DHEA for MILD | | | | | | Omega-3 fatty acids for MILD | | | | | | Saffron, lavender, or roseroot | | | for MILD | +-----------------------------------+-----------------------------------+ | Guided Digital Health | | | Interventions (DHI) | | +-----------------------------------+-----------------------------------+ | - Guided: Good days head, | | | BounceBack, Deprexis, | | | MoodBeacon, Pacifica | | | | | | - Unguided: Catch It, | | | Headspace, MoodGYM, MoodKit, | | | Spark Direct | | | | | | - TLDR: First-line is iCBT | | | guided for MILD or adjunct | | | iCBT for MILD to MODERATE. | | | Rest of lines are adjunct or | | | use when nothing else is | | | available | | +-----------------------------------+-----------------------------------+ | Psychotherapy (not much | | | difference in acute and maintence | | | treatment, evidence for CBT, | | | MBCT, IPT, CBASP, and PST in | | | preventing relapse as well as use | | | of booster sessions) | | +-----------------------------------+-----------------------------------+ | First-line | Cognitive behavioural therapy | | | (CBT), interpersonal therapy | | | (IPT), behavioural activation | | | (BA) | +-----------------------------------+-----------------------------------+ | Second-line | Cognitive behavioural analysis | | | system of psychotherapy (CBASP), | | | Mindfulness-based cognitive | | | therapy (MBCT), Problem-solving | | | therapy (PST), short-term | | | psychodynamic psychotherapy | | | (STPP), transdiagnostic | | | psychological treatment of | | | emotional disorders | +-----------------------------------+-----------------------------------+ | Third-line | Acceptance and commitment therapy | | | (ACT), long-term psychodynamic | | | therapy (PDT), metacognitive | | | therapy (MCT), motivational | | | interviewing | +-----------------------------------+-----------------------------------+ | NOTES: | | | | | | - For most, 12 to 16 sessions | | | indicated with most | | | improvement upfront | | | | | | - Twice weekly in-person CBT or | | | IPT \> weekly | | | | | | - Maintenance psychotherapy can | | | prevent relapse and | | | recurrence, including CBT, | | | MBCT, IPT, CBASP, and PST | | +-----------------------------------+-----------------------------------+ | Pharmacotherapy | | +-----------------------------------+-----------------------------------+ | Initial Choice | | +-----------------------------------+-----------------------------------+ | - Antidepressants reduce | | | suicidal thoughts and | | | behaviours, but suicidal | | | behaviour highest in month | | | before antidepressant | | | initiation and month after | | | discontinuation. | | | | | | - Choose a first-line | | | antidepressant (see notes) | | | based on specifier, symptom | | | dimension, or side | | | effect/tolerability; [wait 2 | | | to 4 weeks for | | | response] | | +-----------------------------------+-----------------------------------+ | Specifier | Symptom Dimension | +-----------------------------------+-----------------------------------+ | - Mixed features | - Cognitive dysfunction  | | | | | | | | | | | - First-line: any first-line | - First line: vortioxetine  | | antidepressant | | | | - Second line: bupropion, | | - Second-line: lurasidone | duloxetine, SSRIs  | | | | | | | | | | | - Psychotic features | - Sleep disturbance  | | | | | | | | | | | - Any first-line + atypical | - First line: agomelatine  | | antipsychotic | | | | - Second line: mirtazapine, | | | quetiapine XR, Trazodone  | | | | | - Catatonic features | | | | | | | - Somatic Symptoms   | | | | | - Benzodiazepine and a | | | first-line antidepressant | | | | - First line: duloxetine | | | (pain), bupropion (fatigue)   | | | | | | - Second line: duloxetine | | | (fatigue), other SNRI (pain), | | | SSRIs (fatigue)   | +-----------------------------------+-----------------------------------+ | Superior Response | - Bupropion, escitalopram, | | | mirtazapine, paroxetine, | | | sertraline, venlafaxine XR, | | | vortioxetine, and agomelatine | | |   | +-----------------------------------+-----------------------------------+ | Most tolerable | - Agomelatine, escitalopram, | | | and vortioxetine | +-----------------------------------+-----------------------------------+ | Least sexual side effects | - Desvenlafaxine, bupropion, | | | mirtazapine, vilazodone, | | | vortioxetine, and agomelatine | +-----------------------------------+-----------------------------------+ | Other considerations | - Interactions: fluoxetine, | | | fluvoxamine, and paroxetine   | | | | | | - QTc prolonging: citalopram, | | | escitalopram, and TCAs   | | | | | | - Discontinuation: paroxetine, | | | venlafaxine XR   | | | | | | - Weight gain: paroxetine and | | | mirtazapine   | | | | | | - Sexual dysfunction: | | | citalopram, escitalopram, | | | fluoxetine, fluvoxamine, | | | paroxetine, duloxetine, | | | venlafaxine-XR   | | | | | | - Increase in BP: SNRI  | | | | | | - Anticholinergic: TCAs, | | | nortriptyline least | | | anticholinergic of the bunch | | | | | | - Bleeding: SSRIs with NSAIDs | | | increase risk of GI bleeds as | | | SSRI inhibit platelet | | | aggregation by altering 5HT | | | platelet receptors, use with | | | PPI to mitigate   | | | | | | - Liver injury: all can cause, | | | but agomelatine, bupropion, | | | duloxetine, and nefazodone | | | are higher risk   | | | | | | - Life threatening in overdose: | | |   | | | | | | - TCA: altered mental | | | status, cardiac toxicity, | | | and seizure   | | | | | | - MAOis: life threatening | | | interactions when used | | | with agents that alter | | | monoamine metabolism (ie. | | | Serotonin reuptake | | | inhibitors, herbal | | | remedies, food with | | | tyramine (cured meats, | | | mature cheeses, and | | | fermented products)   | +-----------------------------------+-----------------------------------+ | Good Response | | +-----------------------------------+-----------------------------------+ | - \*\*Important as risk of | | | recurrence increases with | | | each depressive episode | | | | | | - Maintain pharmacotherapy at | | | lowest dose needed to achieve | | | remission | | | | | | | | | | | | - Continue for 6 to 12 months | | | | | | - Continue for 2 years or more | | | if have following risk | | | factors | | | | | | - Persistent residual | | | symptoms | | | | | | - History of childhood | | | maltreatment | | | | | | - Severe or chronic | | | depressive episodes | | | | | | - Presence of medical | | | comorbidities | | | | | | - Greater number of | | | previous episodes | | | | | | - Poor social support | | | | | | - Persistent stressful life | | | events | | | | | | | | | | | | - Maintain psychotherapy (ie. | | | Booster sessions) or initiate | | | sequential therapy treatment | | | to address residual symptoms | | | and increase well-being (esp. | | | important for severe | | | episodes) | | | | | | - Discontinuing antidepressants | | | | | | | | | | | | - Up to 50% experience | | | discontinuation symptoms | | | (FINISH- flu-like, insomnia, | | | nausea, imbalance, sensory | | | disturbance, and | | | hyperarousal) | | | | | | - No sufficient evidence for | | | schedule, taper gradually | | | over several weeks and extend | | | time between dose reductions | | | near end of taper | | | | | | - Can consider switch to | | | fluoxetine due to long | | | half-life | | | | | | - Rare, but some individuals | | | have severe and irreversible | | | symptoms beyond 6 weeks | | | | | | - Consider hyperbolic tapering | | | (taper by fixed percentage), | | | but not enough evidence for | | | CANMAT recommendation | | +-----------------------------------+-----------------------------------+ | Risk of Discontinuation | | +-----------------------------------+-----------------------------------+ | High | - Paroxetine | | | | | | - Venlafaxine | +-----------------------------------+-----------------------------------+ | Moderate | - TCAs and MAOis, along with | | | other antidepressants | +-----------------------------------+-----------------------------------+ | Low or minimal | - Agomelatine | | | | | | - Bupropion | | | | | | - Fluoxetine | | | | | | - Mirtazapine | | | | | | - Vortioxetine | +-----------------------------------+-----------------------------------+ | Poor Response | | +-----------------------------------+-----------------------------------+ | - 50% achieve response in 8 | | | weeks, 1/3 achieve full | | | remission, and only ¼ of | | | non-remitters who receive a | | | second agent will reach | | | remission | | | | | | - Difficult to treatment | | | depression (DTD)/treatment | | | resistance (TRD): failure to | | | respond to 2 or more | | | antidepressant trials | | | | | | - Factors contributing to poor | | | response | | | | | | - Clinical | | | | | | - Demographic and | | | illness | | | characteristics: | | | older age, female | | | sex, younger age of | | | onset, high severity, | | | increase | | | number/duration of | | | episodes, trauma hx | | | | | | - Comorbid medical or | | | psychiatric illness | | | | | | - Stressors | | | | | | - Treatment factors | | | | | | - Pharmacogenetic | | | variability | | | | | | - Inadequate dose or | | | duration | | | | | | - Side effects masking | | | as symptoms | | | | | | - Poor adherence | | | | | | - If no early improvement (20% | | | or greater score reduction) | | | by 4 weeks, there is low risk | | | of response going forward, | | | with some studies suggesting | | | that lack of improvement in 2 | | | weeks is cause for concern | | | | | | - Steps: | | | | | | 1. Optimize dose (if | | | subtherapeutic dosage or | | | partial response) | | | | | | - Optimize dosage to above | | | minimal therapeutic dose (to | | | a plateau around the | | | equivalent of 50 mg of | | | fluoxetine) | | | | | | 2. Switch antidepressant OR add | | | adjunct | | | | | | 3. Neuromodulation | | +-----------------------------------+-----------------------------------+ | Switching Antidepressants | | +-----------------------------------+-----------------------------------+ | - Diminishing responses beyond | | | first switch | | | | | | - First line: Consider | | | antidepressant with different | | | mechanism of action | | | (marginally more evidence) OR | | | one with evidence for | | | superior efficacy | | | | | | - Second line: Consider a TCA | | | or MAOi | | | | | | - TCA | | | | | | - Nortriptyline has fewest | | | anticholinergic and | | | hypotensive effects, | | | consider for elderly and | | | post-stroke depression | | | | | | - Evidence for superior | | | efficacy in treatment | | | resistant depression | | | | | | - Amitriptyline helpful for | | | comorbid pain conditions, | | | clomipramine for comorbid | | | OCD | | | | | | - Use serum levels to help | | | adjust | | | | | | - MAOis | | | | | | - Requires 2 week washout | | | from antidepressant, 5 | | | weeks if fluoxetine | | +-----------------------------------+-----------------------------------+ | Adjunct | | +-----------------------------------+-----------------------------------+ | A screenshot of a medical chart | | | Description automatically | | | generated | | | | | | - Greater evidence for efficacy | | | and shorter time to response, | | | but greater side effect | | | profile | | | | | | - Only adjunct to an | | | antidepressant if there is | | | partial response as will help | | | retain treatment gains | | | | | | - Atypical Antipsychotics | | | | | | - Most consistent evidence, | | | most downgraded due to | | | side effects (quetiapine | | | = sedation and metabolic | | | side effects, olanzapine | | | = weight gain and | | | metabolic side effects, | | | risperidone = | | | hyperprolactinemia, | | | sexual side effects, and | | | EPS) | | | | | | - All carry risk of TD and | | | mortality in older | | | individuals | | | | | | - 2^nd^ Antidepressant | | | | | | - More tolerable but less | | | evidence for efficacy | | | (ie. California rocket | | | fuel -- venlafaxine and | | | mirtazapine) | | | | | | - Glutamate modulators (see | | | CANMAT 2021 Ketamine section | | | for details) | | | | | | - Off-label IV racemic | | | ketamine x 1 dose, with | | | emerging evidence for | | | repeat infusion (growing | | | evidence for maintenance | | | every 1 to 4 weeks) | | | | | | - CANMAT 2021 Ketamine: | | | IV racemic ketamine | | | as a single infusion | | | Level 1 Evidence for | | | TRD, evidence for | | | multiple infusions, | | | acute series, or | | | maintenance is Level | | | 3 | | | | | | - Intranasal esketamine | | | approved as add-on to | | | SSRI or SNRI after two | | | adequate trials of | | | antidepressants | | | | | | - Rapid reduction in SI, | | | anti-suicidal effects | | | extend for 1 week after | | | infusion | | | | | | - Requires BP monitoring | | | and dissociative side | | | effects | | | | | | - Stimulants | | | | | | - Modafinil has most | | | consistent evidence but | | | small effect size | | +-----------------------------------+-----------------------------------+ | Neuromodulation | | | | | | Note: CANMAT algorithm suggests | | | after psychotherapy and | | | pharmacotherapy failure due to | | | feasibility issues (ie. Patient | | | burden, limited availability etc) | | +-----------------------------------+-----------------------------------+ | First-line | - Electroconvulsive therapy | | | (ECT) for severe MDE | | | (psychosis, catatonia, severe | | | SI, or physical condition | | | deteriorating) | | | | | | - Repetitive transcranial | | | magnetic stimulation (rTMS) | | | for TRD | +-----------------------------------+-----------------------------------+ | Second-line | - ECT for DTD | +-----------------------------------+-----------------------------------+ | Third-line | - Adjunctive use of | | | transcranial direct cranial | | | stimulatioun (tDCS)for | | | mild-moderate MDE | | | | | | - Vagus nerve stimulation (VNS) | | | for DTD | +-----------------------------------+-----------------------------------+ | Investigational | - Deep brain stimulation and | | | Magnetic seizure therapy | +-----------------------------------+-----------------------------------+ | ECT | | +-----------------------------------+-----------------------------------+ | - Delivers electrical stimulus | | | via electrodes on scalp, | | | resulting in induction of | | | brief generalized seizure | | | | | | - Performed under general | | | anesthesia with muscle | | | relaxant | | | | | | - Response rate of 65 to 75%, | | | with reduced risk of suicide | | | 1 year after discharge |