Drugs for mood disorder Flashcards
Conditions that one should be aware of for prescribing antidepressants
Renal/hepatic impairment
Coronary artery disease - avoid TCAs
Epilepsy - lowered seizure threshold
Bipolar - mania
GI bleeding/NSAIDs - avoid fluoxetine, sertraline, paroxetine
MAO-I/Lithium + SSRI –> serotonin syndrome
Alternative antidepressants for GI bleeding
Prescribe gastroprotection (PPI, antihistamine) w/ SSRI
Alternatively use mirtazapine or nortriptyline
Effect of medication on suicide risk
Li –> lower suicide risk
SSRI may initially raise suicide risk in young patients, need regular f/u + management plan
Effectiveness of antidepressant therapy
65-75% of patients (STAR*D trial)
1/3, 1/3, 16%
Monoamine theory of depression
Depression is caused by reduction in monoamines (5-HT, NA, DA)
Antidepressants raise monoamines (resisted by autoreceptor feedback) –> raise BDNF postsynaptically –> neurogenesis/new synaptic connections (explains lag)
Examples of SSRIs
Citalopram
Fluoxetine
Paroxetine
Sertraline
Fluvoxamine
Common side effects of SSRIs
Nausea
Agitation (esp younger patients)
Insomnia
Sexual dysfunction
Postural hypotension
P450 inhibition –> check drug interactions
Discontinuation syndrome (rare but well-characterised)
Examples of SNRIs
Venlafaxine
Duloxetine
Anti-depressants with half-life <24h
Paroxetine
Fluvoxamine
SNRIs e.g. venlafaxine
NDRIs (e.g. buproprion)
Mechanism of action of tricyclic antidepressants
Serotonin + noardrenaline + melatonin presynaptic transporter inhibition
Examples of TCAs
Nortriptyline
Amitryptiline
Clomipramine
Imipramine
Amoxapine
Doxepin
Examples of MAO-Is
Moclobemide (reversible)
Phenelzine (non-reversible)
Common interaction of MAO-I
Tyramine (wine, cheese, chocolate) or sympathomimetic drugs (e.g. decongestants) –> flushing + hypertensive crisis
Drug class of bupropion
Noradrenaline dopamine reuptake inhibitor (NDRI)
Also used for smoking cessation
Drug class of mirtazapine
NAergic and specific serotonin antagonist (NaSSA)
Mechanism of action of NaSSA
Blocks negative feedback –> increase NA and 5-HT release
NA and serotonergic specific antidepressnt
Short-term side effects of SSRIs
Dry mouth
Postural hypotension
GI disturbance
Insomnia
Tremor
Long-term side effects of SSRIs
Platelet dysf(x)
Sexual dysf(x)
Hyponatraemia
SSRI side effects in pregnancy
Increased risk of post-partum haemmorhage
Increased risk of persistent pulmonary hypoplasia (3 per 1000)
Withdrawal symptoms in baby –> increase length of hospital stay but not permanent
TCA contraindications
Neuro: Epilepsy, glaucoma
Psych: Suicidality (dangerous in OD)
Cardiovascular: Recent MI, heart block, arrhythmia, ischaemic heart disease
Endocrine: Prostatism, diabetes (use caution)
TCA toxicity
Prolonged QT, tachyarrhythmias
Seizures
Serotonin syndrome
Common side effects of TCAs
Anticholinergic: ++ (esp dry mouth/eyes, urinary retention/constipation)
Antihistaminergic: +++ (esp sedation, weight gain, advice on driving/machinery)
Cardiac: ++ (toxicity)
Metabolic/neuro: +
MAO-I mode of action
Inhibit MAO –> prevent breakdown of monoamines in presynaptic terminal + synaptic cleft –> raise levels
MAO-I indications
Third-line treatment, for atypical depression
Evidence of lower efficacy
Common side effects of MAO-Is
Postural hypotension
Weight gain
Insomnia
Ankle oedema
Sexual dysfunction
Preferred antidepressant class for cardiac pts
SSRIs (beware antiplatelet drugs)
Antidepressant class if sexual dysf(x) is an issue
Bupropion, mirtazapine
Seratonin syndrome features
Autonomic: Shivering, sweating, hyperthermia,
Cardiac: vasoconstriction/hypertension, tachycardia
GI: nausea/diarrhoea
Neuro: Headache, agitation, confusion, hallucinations
Muscular: Myoclonus, clonus, hyperreflexia, tremor
Management of serotonin syndrome
Fluids: Cause of mortality
Temperature control: cooling blankets, antipyretics
Muscle relaxant: Lorazepam
Rare but dangerous complication of mirtazapine
Agranulocytosis
Look for sore throat, stomatitis, fever, other infx acccompanied by neutropaenia
Distinguishing NMS from SS
NMS:
- Slow onset
- Slow progression
- Lead pipe rigidity
- Bradkinetic activity (cf clonus, tremors)
Prevalence of antidepressant discontinuation syndrome
30%
Timecourse of antidepressant discontinuation syndrome
Abrupt onset (2-5d after withdrawal) + short duration of symptoms (1d -3 weeks), usually self-limiting
Risk factors for antidepressant discontinuation syndrome
Personal: Young age, Hx of discontinuation
Medication: Short half-life (e.g. paroxetine), high dose, duration <8wk, variable compliance
Symptoms of discontinuation syndrome
SD GASS
Sensory: Paraesthesia, visual disturbance
Disequilibrium: Light-headedness, dizziness
both of the above less common with TCAs
GI: nausea + vomiting, diarrhoea
Affective: Irritability, low mood
Sleep: Insomnia, nightmares
Somatic: Flu-like symptoms, fatigue + headache
Proposed mechanism of action of litihium
Substitute for many cations–>??
Effect on membrane electrophysiology
Gene expression –> neuroprotective
Effect on 2nd messenger systems (e.g. lower inositol levels)
Drug interactions for Lithium
Cardiovascular: Anti-arrhtyhmics, anti-hypertensives
Analgesics esp NSAIDs
Psychiatric: Antipsychotics, antidepressants, antiepileptics
Antacids
Workup before starting Lithium
Weight
U+Es + Ca, eGFR
TFTs
ECG
FBC
Advise commitment >=2y necessary
Lithium level monitoring
1w after starting Li
1w after every dose change, weekly until stable levels
Every 3mo Li levels + TFTs/renal f(x)/ECG/BMI/U+E (incl. Ca)
Common side effects of Lithium
Early: Metallic taste, dry mouth, thirst, polyuria, fine tremor, cognitive problems
Late: Weight gain + sedation, psoriasis, hair loss
Rarer but more dangerous side effects of lithium
Hypothyroidism (1/20)
CKD (1/10 reversible, 1% irreversible)
Slowed cardiac conduction leading to arrhythmias (contraindicated in heart failure/sick sinus)
Risk of congenital anomalies in Li pregnancies compared to normal
4-12% vs 2-4%
Signs of Li toxicity
Early: Coarse tremor, diarrhoea (often bloody), dehydration, lethargy, N+V
Late: Ataxia, slurred speech, muscle hypertonicity/fasciculations, confusion/delirium
Management of Li toxicity
Education: Stay hydrated + eat enough salt esp on hot days
Dose modification: + level monitoring
Emergency: Isotonic saline resuscitation to force diuresis
Psychiatric indications for valproate
Acute mania
Depressive episode of bipolar alongside antidepressant
Bipolar prophylaxis (unlicensed)
Mechanism of action of valproate
Increase GABAergic availability
Absolute contraindication for valproate
Females of child-bearing age
Common side effects of valproate
GI disturbance
Sedation, headache
Ataxia, tremor
Thrombocytopaenia –> manage bleeding risk esp before surgery
Rarer but more serious side effects of valproate
Pancreatitis
Hepatotoxicity
Agranulocytosis
Psychiatric indications for lamotrigine
Prophylaxis for bipolar disorder, prevents depressive episodes
Mechanism of action of lamotrigine
Inhibits voltage-gated Na channels, reduces glutamate release
Common side effects for lamotrigine
N+V
Sleepiness/insomnia
Visual + cerebellar dysf(x)
Rarer but more dangerous side effects of lamotrigine
Rash (3-5%) - stop at first sign due to risk of SJS/TEN
Hepatotoxicity
Blood dyscrasias
Timing of TCA and SSRI medication
SSRI: morning as activating
TCA: night as sedating (avoid in people who need to drive/use heavymachinery esp in the early morning)
Antidepressant class of choice for post-MI depression
SSRIs, antiplatelet effect may be protective against CV risk
Monitoring antidepressants
Every 1-2 weeks
Screen for hyponatraemia, SE profile, suicidality, serotonin syndrome
Monitoring for valproate
LFTs
Mood stabilisers for Li-resistant bipolar
Lamotrigine
Sodium valproate
Carbamazepine (less effective)
Common side effects of SNRIs
Hypertension
Common side effects of mirtazapine
Antiemetic, antipruritic, sedating
Oversedation, hyperphagia
