Affective disorders Flashcards
How is depression categorised?
-More Severe - PHQ-9 <16
-Less severe - PHQ-9>16
What is used to classify depression?
PHQ-9
1st line treatment for depression?
SSRIs (sertraline)
What is the mode of action of SSRI?
-Selectively inhibit synaptic 5-HT re-uptake transporters, thereby increasing synaptic 5-HT concentration
What is a good first choice SSRI and why?
-Sertraline 50-100mg daily going up to 200mg daily
-it is well tolerated and has fewer interactions compared to other drugs
What SSRI is most useful post myocardial infarction?
Sertraline
Give other examples of SSRIs
-Citalopram
-Fluoxetine (children and adolescents)
-Paroextine
what is the most common side effects of SSRIs?
-GI symptoms are most common side effect
NSAID and SSRI?
Prescribe PPI, increase risk of bleeding
Counselling before SSRI?
Increased anxiety and agitation after SSRI
What SSRIs have higher propensity for drug interactions?
Paroexteine and fluoxetine
What is citalopram associated with?
-Dose dependent QT interval prolongation
When should citalopram not be used?
-Congential long QT syndrome
-Known pre-existing QT interval prolongation
-Combination with other medicines that cause prolong QT interval
What is the maximum dose of citalopram in adults?
40mg
What is the maximum dose of citalopram in patients >65 or with hepatic impairment ?
20mg
If warfarin/heparin what other medication should you consider?
Mirtazapine
Aspirin with SSRI?
Increased risk of bleeding
What drugs SSRIs increase the risk of serotonin syndrome?
-Triptans
-MAOIS
-Lithium
-St Johns wort
What are the discontinuation symptoms of SSRIs?
-Increased mood change
-Restlesness
-Difficulty sleeping
-Unsteadiness
-Sweating
-GI symptoms
-Paraesthetisa
What SSRI has increase risk of congenital malformations?
Paroxentine
What SRRI is more toxic in overdose?
Citalopram - avoid in people with suicide ideation
What are the two SNRIs?
-Venlafaxine (75-375 mg)
-Duloxetine (60 mg)
What is the mode of action of SNRIs?
-Inhibit reuptake serotonin and noradrenaline in synaptic cleft
-Increase concentration of NA and serotonin
-SNRIs do noot block cholinergic receptors
Why are SNRIs useful?
-Venlafaxine is thought to be slightly more effective then SSRIs (but not duloxetine)
-Main indication is for a non-SSRI response
Side effects of SNRIs?
-Resembles those of SSRI but may be worse
-At high doses hypertension can occur and should be monitored
What drug is a noradrenaline and serotonin specific antidepressant (NASSA)?
-Mirtzapine (15-45mg)
What is the mode of action of mirtazapine?
Increase the activity of NA and 5-HT systems
-It blocks the negative feedback on NA presynaptic alpha-2 receptors
-Alpha 2 blockade also enhances 5-HT release
When is the NASSA mirtazapine practically useful?
-2nd line treatment
-In combination with SRRI for third line treatment
What are the side effects of NASSA mirtazapine?
-Relatively sedating so can be useful in those with sleep issues
Side effects of NASSA mirtazapine?
-Can be associated with weight gain
What is the mode of action of TCAs?
-Inhibit PRESYNAPTIC NA and 5-HT transporters
-Some TCAs are more selective for one monoamine than another e.g. clomipramine mainly acts on 5-HT and desipramine on NA
Why are TCAs less commonly used now?
-Side effects as they block various other receptors unlike SSRIs
-Toxic in overdose
Where might TCAs be useful?
Widely used in treatment of neuropathic pain - however smaller doses are required
how do other receptors impact TCAs side effect profile?
- Antagonism of histamine - drowsiness
-Weight gain - Antagonism muscarinic receptors
-Dry moth
-Blurred vision
-Consitpation
-Urinary retention
-Tachycardia - Antagonism of adrenergic receptors
-Postural hypotension
-Sexual dysfunction - Lengthening of QT interval
Examples of more sedative TCAs
-Amitriptyline
-Clompramine
-Dosulepin
Examples of less sedating TCAs
-Impramine
-Lofepramine
-Notriptyline
What TCA is used commonly used in the management of neuropathic pain and prophylaxis of headache?
-Tension headache and migraine
-Also can be used for insomnia
What TCAs are considered the most toxic?
-Amitriptyline
-Dosulepin
Why is mirtazapine (NASSA) good for older people?
-Fewer side effects and interaction than many other antidepressants so can be useful in older people that are taking multiple medications
-Two side effects - increased appetite and sedation so useful insomnia and poor appetite
Mode of action of MAOIs (monoamine oxidase inhibitors)?
-Serotonin and NA are metabolised by monoamine oxidase in presynaptic cell
-MAOIS prevent the breakdown of monoamines in the presynaptic terminals
-Increase transmitter availability
Examples of MAOI?
-Tranylcypromine (10-30mg a day)
-Phenelzine (15-90mg)
MOI compared to SSRI and TCA?
Due to side effects and efficacy are seen inferior
When can MOI be useful in depression?
-The main induction is atypical depression
-Can be used in treatment resistant depression
What is atypical depression?
-Increased sleep
-Increased appetite
-Phobic anxiety
What are the side effects of MAOIS?
-Hypertensive reactions with tyramine containing foods e.g. cheese, pickled herring, Bovril, oxo, marmite , broad beans
-Anticholinergic effcets (dry mouth, blurry vision, drowsiness, sedation)
When to avoid MAOIs?
Cardiac failure, hepatic failure
Overdose MAOIs?
-Hypertension, delirium, coma and death
Risk associated with each antidepressant?
Risks
1.Drug interaction - fluoxetine, fluvoxamine, paroxetine
2.Discontinuation Symptoms: paroxetine
3.Death from Overdose: venlafaxine
4.Overdose: TCAs (except lofepramine)
5.Stopping due to side effects: venlafaxine, duloxetine, TCAs
6. Blood Pressure Monitoring Needed: venlafaxine
7. Worsening Hypertension: venlafaxine, duloxetine
8. Postural Hypotension and Arrhythmia: TCA
Switching from fluoxetine to other antidepressants?
NICE recommends a washout period of 4-7 days with NO antidepressant before starting a low dose of another SSRI
Switching form fluoxetine or paroxetine to a TCA?
Both drugs inhibit TCA metabolism so a lower starting dose may be needed to reduce risk of serotonin syndrome
From non-reversible MAOI?
A 2-week washout period is required (other antidepressants should not be prescribed during this period)
How common is it for a depressive episode to not respond to first-line treatment?
2/3 cases do not respond to 1st line antidepressant
What to do when patient has not improved when given antidepressant?
-Check compliance
-Increase to maximum dose tolerated
-Review the case - is the diagnosis right?
If patient has not improved after compliance checked, the diagnosis is correct and is on the maximum dose?
-Switch SSRI to different SSRI or SNRI 9limited evidence with either strategy )
-If depression is severe add lithium (risks and drawback limit popularity)
-Add mirtazapine if insomnia or agitation is the issue
-Add CBT
-Add second generation antipsychotic (quetiapine or olanzapine) especially if psychotic symptoms or agitation or insomnia
-Psychiatric referral if not already occurred
When to refer psychiatry for depression?
-Not responding to treatment
-Substansital risk to self or other
-Second option of diagnosis
-Combination or rare agent being considered
-Patient severely unwell and hospital admission is required such as ECT
Hyponatrameia and SSRI?
Can occur in elderly possibly due to inappropriate secretion of ADH
How long should patent continue antidepressant treatment?
For at least 9 months
Peventing relapse in patient?
How much does continuation of antidepressant after recovery prevent relapse?
by at least 50% in patient with recurrent depressive episode
What is bipolar disorder?
Replacing and remitting condition characterised by presence of periods of elated mood and depressed mood - however presence of elated mood alone is sufficient for diagnosis to be made
Features of hypomania ?
-Present for at least 4 days
-Core features mild or moderate
-mild or moderate dysfunction
-Patiral insight persevered
-No psychotic features
Features of mania?
Present for at least 7 days needing hospital admission
-Core features marked
-Substantial dysfunction
-Minimal or absent insight
-Psychotic symptoms may occur
Heritability of bipolar disorder?
Strongly heritable - 80%
When are benzodiazepines used in bipolar?
Useful when sedation is required
Treatment of mania and mixed episodes of bipolar?
-Antipsychotics such as risperiodone, olanzapine
-Valporate and lithium are antimanics
Antipsychotics and lithium effectiveness?
Antipsychotics probably more effective but cause more sedation and weight gain
Mania not responding to drug treatment?
ECT highly effective
Antidepressant in manic episode?
Stop antidepressant
Promodal symptoms of mania?
Sodium valproate can be useful
Treatment of depressive episode in bipolar?
-Quetiapine - an atypical antipsychotic is the first line treatment
-Rapid onset of action
NOTE: antidepressants may be less effective as they can precipitate mood destabilisation and mania
What limits quetiapine long term use?
Sedation and weight gain
Preventing relapse in bipolar disorder?
-Patient needs to understand own illness
-Long term mood monitoring
-Relapses in bipolar disorder due to non-specific symptoms - helpful if patient recognisises these warning signs
When is going term drug treatment recommended in bipolar disorder?
-At least two manic episodes
- one manic and one depressive episode
NOTE: effective early treatment may improve long term outcome so usually long term treatment is after one serious episode especially if family history
What is the standard prophylaxis of bipolar disorder?
-Lithium treatment is the gold standard for bipolar disorder
-Reduces the risk of manic and depressive relapse by 40-50%
What are organic mood disorders?
mood disorders with a physical cause
Three main drugs used in mania?
-Lithium
-Sodium valproate
-Carbamazepine
What is the therapeutic range of lithium?
0.6-1.0mmol/L
Dose for lithium naive patients?
0.6-0.8
Dose for patients with previous lithium use or relapse in symptoms?
0.8-1.0
What range does lithium toxicity occur?
-1.5mmol/L
-Severe 2mmol/L
Blood before starting lithium?
-BMI
-FBC
-Uand E
-TFTs
When should plasma lithium be checked?
-1 week after starting and changing dose
-monitored weekly until steady therapeutic level achived
NOTe: blood sample 12 hours after taking lithium dose
how often should lithium levels be measured when stable levels reached?
-Every 3 months
Why should U&Es and TFTs be monitored every 6 months?
-Lithium can cause renal impairment and hypothyroidism
What are the signs and symptoms of lithium overdose?
- GI disturbance
- Polyuria/polydipsia
- Sluggishness or giddiness
- Ataxia
- Gross tremor
- Seizures
- Renal failure
What can trigger lithium toxicity?
-Salt balance and electrolyte changes
-Drugs interfering with lithium excretion (diuretics and NSAIDs)
-Overdose
How to manage lithium overdose?
-Stop lithium (note that can precipitate mania/depression)
-Medical care (rehydration and osmotic diuresis)
-Overdose severe - gastric levage
When is sodium valproate used?
-Treat acute mania
-Prophylaxis is BPAD
Benefits of using sodium valporate over lithium>
-Plasma levels do not need monitoring
-Dose-related toxicity is not usually an issue
What should you check before starting sodium valproate?
BMI, FBC, LTFs
What is carbamazepine?
An anticonvulsant
what percent of women get hypothyroidism from lithium?
20%
Contraindication of lithium use?
-Avoid in renal failure and pregnancy
-Do not combine with diuretics, ACE inhibiors or high dose antipsychotics
-Be cautious with NSAID use (can rise lithium levels)
Practical use of sodium valporate?
Has a place where lithium is not tolerated
What is the dosing of sodium valporate?
-Usually maintenance dose 750-1250mg but starting dose is lower 250-500mg
What are the side effects of sodium valporate?
-Sedation
-Tiredness
-GI distrubances
-Can cause thrombocytopenia
-Reversible hairloss in 10% patients
What does sodium valporate cuase in pregnancy?
-Associated with neural tibe defects
-Spina bifida
Carbamazepine for bipolar disorder compared with sodium valproate and lithium?
-Thought to be less effective than both
-May be used when contraindicated, ineffctive or not tolerated
How does sodium valporate work?
Blocking sodium channels and increasing GABA turnover
If signs of toxicity with carbamazepine uses?
-Check plasma levels
What levels should you check in carbamazepine uses?
-White blood cells - can cause low white blood cells
What are the side effects of carbamazepine?
-Leucopenia
-Dizziness
-Drowsiness
-Hyponatreamia
Why is the fact that carbamazepine induces liver enzymes significant?
-other drugs are metabolised faster such as the contraceptive pill
When to stop carbamazepine?
-Erythematous rash
-Leucoytopenia
When is lamotrigine useful in bipolar disorder?
-When treating a depressive episode
-is second line for prophylaxis in BPAD typeII
What is the mode of action of lamotrigine?
-Blocks calcium and sodium channels
-Decreases glutamate release
Dose of lamotrigine in bipolar?
-100-300mg
-Start 25 mg 2 weeks, then 50 mg two weeks
-Gradual increase reduces side effects
side effects of lamotrigine?
-rash - discontinue
-Stevens-Johnson syndrome/toxic epidermal necrolysis
Valporate and lamotrigine?
-Valporate increases lamotrigine levels causing neurotoxcity be cauitious
Childbrearing age and valporate
-Contraceptive advice
-Folate supplement
mood stabilizers in pregnancy?
-Teratogenic
-Risk of harm vs risk of manic relapse
-Closely monitor fetus
Acute treatment of mania or hypomania?
-Stop all medications that induce symptoms
-Give antipsychotic and short course of benzodiazepines
What may be used if patients are unresponsive to medication in bipolar disorder?
ECT
Long term treatment of bipolar disorder?
-Mood stabilizers are the mainstay
-Antipsychotica or benzodiazepines can be added when new symptoms arise or stress
Depression in BPAD?
1st line: FLuoxetine and olanzepine/quetiapine
2nd line: lamotrigine
How to refer if symptoms of hypomania?
-Routine referal to CMHT
How to refer if mania or severe depression?
urgent referral
Medication for overdose on opiod?
Naloxone
Overdose of other medication e.g. antidepressants?
-Activated charcoal
-Use less one hour ingestion
What can be used for paracetmol overdose?
-N-acetylcystine
Contraindication for ECT therapy?
-Mainly related to anesthetic risk
-Avoid if patient has intracranial lesion
Prolonged grief?
Prominent symptoms more than 6-12 months
Excessive grief?
> 12 months, may reflect persons closeness, personality or depressive disorder
