Depression Flashcards
List some DDx for depression?
Neurological:
- neurodegenerative disease (e.g. Alzheimer’s, Parkinson’s)
- SOL
- malignancy
- collagen vascular disease (e.g. SLE)
Non-neurological:
- Endocrine (e.g. DM, Cushings syndrome, Addison disease, hypo/hyperthyroidism, hypo/hypercalcaemia)
- CKD
- anaemia
- malignancy (esp. lymphoma and pancreatic ca)
- viral illness (e.g. mononucleosis)
- medications (e.g. steroids, antihypertensives, B-blockers, Parkinson’s Rx)
Psychiatric:
- major depression
- bipolar affective disorder (depressive episode)
- schizophrenia
- schizoaffective disorder
- post-partum depression
- PTSD
What is known about the pathogenesis of depression?
Path:
- large life event or environmental stressor -> first episode -> brain biology change -> neurotransmitter change, signalling systems and neuronal loss -> risk second episode
- neurotransmitters most implicated are noradrenaline and serotonin, also dopamine and ACh
Risks:
- OCD, borderline personality disorders
- stopping antidepressants < 3/12 (risk relapse)
What is the diagnostic criteria for depression?
DSM V depression criteria: >2 weeks of depressed mood and 5 symptoms causing significant functional impairment (SIGECAPS mnemonic): - S- sleep increased - I -interest decreased - G- guilt increased - E - energy decreased - C - concentration decreased - A - anhedonia - P- psychomotor symptoms - S- suicidal ideation
What is the treatment for depression?
Acute: asses risk of safety to self and others, ideation
Non-pharmacological:
- exercise
- sleep deprivation (alleviate depressive episode, trigger manic)
- phototherapy
- reducing life stressors (social, financial, work)
Pharmacological:
- SSRI, Noradrenergic and specific serotonergic antidepressants (NaSSAs), NDRIs, SNRIs, melatonin agonist, serotonin modulator
- TCAs, MAOIs
- ECT
Describe the MAO of SSRIs?
Selective serotonin reuptake inhibitors (SSRIs):
- E.g. Sertraline/Zoloft, Fluoxetine/Prozac, Paroxetine/Paxil, Citalopram
- MA: inhibits presynaptive 5HT reuptake pumps -> increasing amount of serotonin in synaptic cleft
- Also causes weak
inhibition of NA, DA with some adrenergic, histamine and muscarinic effects
Note: depression MA: functional deficit of serotonin (5HT) and noradrenaline (NA)
- Takes 4-6 weeks to work
- Cessation: must be weaned due to discontinuation syndrome (headaches, anxiety)
List some SE of SSRIs?
SE:
- CVS: orthostatic hypotension
- Sexual dysfunction: decreased libido, anorgasmia (LTM)
- Loss of appetite and weight
- GIT: nausea, diarrhoea, bleeding (blocks uptake of serotonin into platelets), liver or renal impairment
- Neuro: headache, dizziness, insomnia, sedation, anxiety, tremors, akathisia, suicidal ideation
- hyponatraemia
- sweating
- reduced ETOH tolerance
- Serotonin syndrome (if combined with TCA, MAOI, SNRIs, other SSRIs, can be fatal) -> headache, confusion, hallucinations, seizures, coma, tachycardia, myoclonus, hyper-reflexia, tremor, rhabdomyolysis, renal failure
Describe the MAO and SE of SNRIs?
Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
(e. g. Venlafaxine)
- MA: inhibition of NA and 5HT reuptake, little activity on H1, M and a1 receptos
- Lower SE profile than TCAs
- SE: similar to SSRIs, headaches, anticholinergic effects
Cessation: discontinuation syndrome (headaches, anxiety)
Describe the MAO and SE of TCAs?
Tricyclic antidepressants (TCAs) (e.g. Nortriptyline, amitriptyline)
- MA: inhibition of 5HT and NA reuptake, some dopamine reuptake inhibition
- SE: sedation, weight gain, anti-cholinergic effects (dry mouth, blurred vision, urinary retention, constipation), QT prolongation, seizures, orthostatic hypotension
- Serotonin syndrome (if combined with MAOI, SNRIs, SSRIs, can be fatal)
- Used less commonly due to SE profile
- Toxicity: lethal in overdose
Describe the MAO and SE of MAOIs?
Monoamine Oxidase Inhibitors (MAOIs)
(e.g. Moclebamide)
- MA: inhibit monoamine oxidase -> decreases metabolism of monoamine neurotransmitters (NA,
5HT, adrenaline and DA) -> increasing concentration in pre-synaptic terminals
- SE: weight gain, postural hypotension, anticholinergic effects, hypertensive crisis (due to tyramine consumption e.g. cheese)
- Serotonin syndrome (if combined with TCA, SNRIs, SSRIs, can be fatal)
Describe the MAO and SE of NaSSAs?
NaSSA: Noradrenergic and specific serotonergic antidepressant
Examples: Mirtazapine, Mianserin
- MA: Blocks alpha-2, 5-HT2C and 5-HT3 receptors
- SE: weight gain , anticholinergic, anti-adrenergic
-> Mianserin: agranulocytosis, aplastic anaemia
- No serious drug interactions
What would you prescribe for:
- mild/moderate depression
- mod/severe depression
- psychotic depression
- atypical depression
- anxious depression
Prescription:
- mild/moderate depression: psychotherapy
- mod/severe depression: 1st line SSRI, 2nd line MAOI and TCA
- psychotic depression: TCA + antipsychotic
- atypical depression: MAOI or SSRI
- anxious depression
If severely suicidal or meds fail -> ECT
What advice would you give a pt starting an SSRI?
SSRI examples: Sertraline/Zoloft, Fluoxetine/Prozac, Paroxetine/Paxil, Citalopram
- relatively safer in overdose
- relatively mild SE profile
- MA: blocks serotonin transporter (SERT) -> prevents reuptake of serotonin
- duration: 1-2 weeks to begin working, 4-6 weeks for full effect
(window period of 2-4 weeks suicide risk)
- emphasise compliance importance
- SE: sexual dysfunction, rebound anxiety, GI disturbance/bleed, headache, serotonin syndrome (overdose)
- Interactions: increases CYP450 inhibitors (paracetamol, codeine, steroids, warfarin, anti-arrhythmics, ca-channel blockers)
- Serotonin syndrome (if combined with TCA, MAOI, SNRIs, other SSRIs, and St John’s wart -> can be fatal)
How long do you keep a pt on an SSRI?
- if effective, continue for >6/12, preferably 12/12 after single major depressive episode (high relapse risk)
LTM prohylaxis: 3-5 years: - if hx recurrence (>2 depressive episodes in 5yrs OR 3 prev episodes)
- single episode severe psychotic depression
- suicide attempt
What drug interactions are a concern with SSRIs?
SSRIs -> inhibit the CYP450 enzyme -> reduce metabolism of other drugs -> increase their plasma concentration
- > increase efficacy and complications:
- B blockers
- antipsychotics
- anticonvulsants
- benzos
- warfarin
- cyclosporin
- anti-arrhythmics
- ca channel blockers
Serotonin syndrome: if combined with TCA, MAOI, SNRIs, other SSRIs, and St John’s wart -> can be fatal
If depression improved, would you stop the SSRI?
If within course of therapy (6-12 months) -> would not stop (relapse risk)
If after course of therapy -> history and mental state exam, collateral hx, prev recurrence episodes, pt preference
SSRI discontinuation (withdrawal syndrome):
- withdrawal syndrome more likely at higher dose, longer duration and shorter half-life of Rx
- clinical: insomnia, nausea, headache, anxiety, sensory disturbance, hyper-arousal symptoms, delirium
- method: taper slowly, halve dose each week, monitor carefully, advice family/friends
