Depression

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  • Created by: LBCW0502
  • Created on: 23-12-18 14:47
What is depression?
Described as being stuck at the bottom of a deep dark well. Sides of the well are slippery, almost glass like. Unable to get back up the well and just slide back down the bottom again
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Is depression an increasing problem?
Yes - ranked no. 4 in 1990 (Rank of Global Disease Burden - measure in terms of disability adjusted life years). Unipolar major depression estimated to be ranked at no. 2 in 2020
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Is depression a fatal disorder?
If left untreated, depression increases risk of mortality (death). Suicide more common in depressed patients. 21% of patients with recurrent depressive episodes attempt suicide
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What are the links between psychiatric illness and suicide?
Psychiatric illness (odds ratio for suicide). Bipolar 9.20 (4.38 - 19.33). Depression 6.44 (5.45-7.61). Psychotic conditions 5.09 (3.94-6.59). Anxiety disorders 4.65 (4.07-5.32)
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Describe the epidemiology of depression?
Difficult to give precise figure (difficulties/variations with diagnosis). America/Europe using validated assessment tools to estimate lifetime prevalence of 16% (1 in 6 people). Women > men. Social/economic/ethnic factors have influence
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What are the core symptoms of depression?
Depressed/low mood (tearful). Loss of interest/pleasure (stop activities). Fatigue (tired)
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What are the other symptoms of depression? (1)
Feeling hopeless (lack of confidence of future). Guilty (lack of attention to self-care). Difficulty concentration (unable to do tasks). Unable to sleep. Altered appetite (weight changes)
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What are the other symptoms of depression? (2)
Thoughts of death/suicide (feeling that life is not worth it). Restlessness/irritable (unable to concentrate/stay still). Persistent physical symptoms (headaches, pain etc.)
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What are the emotional symptoms of depression?
Low mood, guilt, worthlessness, suicidal thoughts, reduced confidence
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What are the cognitive symptoms of depression?
Reduced attention, reduced concentration
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What are the behavioural symptoms of depression?
Anhedonia, tearfulness, irritability, anxiety, social withdrawal
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What are the physical symptoms of depression?
Low energy, reduced sleep, reduced appetite, reduced Libido, painful symptoms
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Describe features of the diagnosis of depression
Standards for uniform approach. ICD-10 classifies as mild/moderate/severe. Based on number of symptoms present. Determine treatment options
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What are the symptoms for mild depression?
At least 4 symptoms, 2 of which must be key symptoms - still able to perform majority of functions of life but with little or no enjoyment
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What are the symptoms of moderate depression?
At least 6 symptoms, 2 of which must be key symptoms - only able to perform functions of life with difficulty
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What are the symptoms of severe depression?
At least 8 symptoms, 3 of which must be key symptoms - not able to perform some or all functions of life e.g. unable to get out of bed, go to work, take care of self/family
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Outline features of symptom screening and rating
Systematic rating scales. Validated scales use number of Qs to objectively assess individual depression severity. Scales with smaller number of Qs less sensitive to change (easier/quicker to complete)
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Give examples of scales validated in primary care
PHQ - 9, BDII (Beck Depression Inventory 2nd edition), HADS (Hospital Anxiety & Depression Scale). Some use simple 2 Q test to screen for possible presence of depression
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Describe features of the Two Question Test (simple test)
Yes to either Qs - during the last month have you been bothered by feeling down, depressed or hopeless? During the last month, have you often been bothered by little interest or pleasure in doing things? - lacks specificity, doesn't assess anxiety
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Describe features of the PHQ-9
Self administeredl. Patients assess each of 9 criteria used by DSM-UV for diagnosis of depression. Rated 0 (not at all) to 3 (nearly every day). Score 0-4 (no depression), 5-9 (mild), 10-14 (moderate), 15-19 (moderate-severe), 20-27 (severe)
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Describe features of the HADS
Self administered 14 item rating scale. 7 Qs assess depression, 27 Qs assess anxiety. Designed for hospital general medical outpatients but also used in primary care. <5 mins for completion
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Describe features of BDI-II
Self administered 21 item rating scale. Indicator of depressive symptoms based on DSM-IV criteria. 5-10 mins completion. Rated 0-3, ranges of scores from 0-63. 14-19 (mild), 20-28 (moderate), 29-63 (severe)
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What are the general effects of antidepressant drug therapy?
All antidepressants increase availability of serotonin or noradrenaline in the synaptic cleft (interfere with neurotransmitter synthesis, storage, release, removal/re-uptake, degradation)
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What is the consequence of increases synaptic neurotransmitter?
Antidepressants quickly increase synaptic neurotransmitter levels. Antidepressant effect/mood lift (not seen for 2+ weeks). Acute increases in neurotransmitter levels cause adaptive changes in receptor activity (down regulation/desensitisation
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What does down regulation and desensitisation lead to?
Reducing number and sensitivity of postsynaptic receptors - adaptive changes in receptor number/frequency are likely to result from alterations in gene expression (switching off synthesis of neurotransmitter receptors, increase synthesis of BDNF)
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Describe features of SSRIs
Block pre-synaptic re-uptake of serotonin e.g. fluoxetine, citalopram (escitalopram), paroxetine, sertraline
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What are the common side effects of SSRIs?
Initial increase in anxiety (mechanism). Nausea and vomiting. Headaches. Sexual dysfunction (more prevalent). Occasional movement disorders (e.g. akathisia, tremor), risk of gastric bleeding
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Describe features of SSRIs and gastric bleeding (1)
Risk of GI bleed associated with SSRIs (increased 3 fold). Mechanism - vascular injury stimulates serotonin release by platelet cells, release serotonin promotes vasoconstriction/platelet aggregation by altering platelet shape.
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Describe features of SSRIs and gastric bleeding (2)
Platelets cannot synthesise serotonin, rely on uptake of serotonin into platelet cell by means of SERT. SSRIs block action of SERT which limits platelet serotonin function (patient should take PPI with NSAID and SSRI)
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Describe features of fluoxetine
Greater half life than other SSRIs (up to 140 hrs). Other SSRIs are 24 hrs. Fluoxetine significant inhibitor CYP 2D6 (and 3A4) hepatic enzyme
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Describe features of paroxetine
Associated with greater withdrawal effects (due to inhibition of own metabolism). Significant inhibitor CYP 2D6 (and 3A4) hepatic enzymes
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Describe features of TCAs
Similar chemical structure. Mechanism involves inhibition of monoamine re-uptake by presynaptic neurone
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Give examples of TCAs
Amitriptyline (inhibitor of 5HT/NE reuptake), clomipramine (inhibitor of 5HT reuptake), dosulpine (inhibitor of 5HT-NE reuptake), lofepramine (inhibitor of NE (reuptake)
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What are the side effects of TCAs?
Poor Tolerability. Sedation, anticholinergic (dry mouth, constipation, blurred vision, urinary retention), postural hypotension, tachycardia. Dose needs to start low then increased (amitriptyline 75 mg to 100-150 mg). Effect of ADRs on delayed action
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What are the cardiac effects of TCAs?
Blocks cardiac Na+ channels and some K+ channels. ECG changes (PR/QRS/QT prolongation). Toxicity in overdose (500 mg). Not for patients with cardiac history (apart from rhythm changes TCAs causes - tachycardia, hypotension)
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Which TCA causes minimal cardiac side effects?
Lofepramine
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Describe features of venlafaxine for antidepressant therapy
SNRI. Greater potency for inhibition of serotonin reuptake (low doses <150 mg/day). NE reuptake at higher doses. Poor tolerability
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What are the side effects of venlafaxine?
Nausea, headache/increased anxiety, sexual dysfunction, insomnia, tremor, constipation, dry mouth, blurred vision, postural hypotension, drowsiness (dose at 75 mg/day, increased up to 250 mg/day or 375 mg/day in divided doses/standard release)
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What are the cardiac side effects of venlafaxine?
Cardiac toxicity. Block Na+ channels in cardiac muscle. ECG changes more common. Prescribing restrictions. Issue with dose in hypertension. Use with caution in history of cardiac disease (arrhythmias) not used in those with uncontrolled hypertension
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Describe features of mirtazapine in antidepressant therapy (1)
Mechanism - indirect potentiation of NE/5HT neurotransmission). Presynaptic alpha 2 adrenoceptor antagonist (auto-receptors). NE switches off NE/5HT neurone firing by interacting with pre-synaptic a2 receptors
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Describe features of mirtazapine in antidepressant therapy (2)
Blocking this leads to mirtazapine releasing the 'brake' and causing increased neurotransmission. Better than expected side effect profile
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Describe features of mirtazapine in antidepressant therapy (3)
Antagonist of 5HT2A, 5HT2C, 5HT3 receptors. Mediate serotonergic side effects (sexual dysfunction, appetite disturbance, nausea, gastric upset). Mirtazapine effects unaltered (mediated by 5HT1A receptors)
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What are the side effects of mirtazapine?
Sedation, increased appetite, weight gain, occasional dizziness, headache, agranulocytosis (rare) - dose of 15 mg/day increased up to 45 mg/day
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Give examples of other antidepressants (1)
Agomelatine (selective serotonin receptor antagonist/melatonin receptor antagonist, beneficial effects for sleep, side effects - agitation abdominal pain, nausea, drowsiness, need to monitor hepatic function)
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Give examples of other antidepressants (2)
Duloxetine (similar to venlafaxine/more balanced effect). Vortioxetine (multimodal effect, SSRI, antagonist at 5HT3 and agonist at 5HT1a, antidepressant with anxiolytic effects, side effects similar to SSRIs)
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Describe features of antidepressants and suicide (1)
Suicide could be due to antidepressant or delay in seeking help. After starting antidepressant therapy, mood remains low, but energy and motivation might start to increase, presence of akathisia or increase anxiety may be significant
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Describe features of antidepressants and suicide (2)
Recent data from observational studies cast doubt on whether SSRIs increase suicide in adults with depression - there may be a reduced risk
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Describe the impact of TCAs
Large number of deaths due to TCAs (overdose). Recommendations - those with increased risk of suicide (<30 years) seen more frequently during early treatment. Limited supply of medication (1 week initially). Use antidepressant/low OD toxicity
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Describe features of antidepressant withdrawal reactions (1)
Antidepressants are not addictive. Withdrawal symptoms seen when antidepressants stopped suddenly. Common symptoms - agitation, irritable, flu-like symptoms (chills, myalgia, sweating), shock, dizziness
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Describe features of antidepressant withdrawal reactions (2)
Discontinuation symptoms more likely if - drug has short half life, therapy > 8 weeks, anxiety symptoms exacerbated at initiation, history of discontinuation symptoms. More likely with paroxetine and venlafaxine. Less likely in fluoxetine/citalopram
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What are the recommendations for antidepressant withdrawal reactions? (1)
Inform patients about potential risk of withdrawal reactions, symptoms usually mild/self-limiting, try to stop antidepressant gradually over at least 4 weeks (fluoxetine doesn't require slow cessation)
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What are the recommendations for antidepressant withdrawal reactions? (2)
If mild symptoms appear reassure patient/monitor. If severe symptoms appear recommence antidepressant at previous tolerated dose
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Describe features of antidepressant treatment strategy
Key priorities from NICE CG90 - Depression. Limited evidence in use for antidepressants for mild depression, introduced concept of stepped care. SSRIs (first choice). Need to warn patients about potential of withdrawal reactions. (NICE website)
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Outline the stepped care in depression treatment
Step 1 - recognition in primary care/general hospital settings. Step 2 - treat mild depression in primary care. Step 3 - treatment of moderate-severe depression in primary care. Step 4 - treatment by mental health specialists. Step 5 - inpatient care
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Describe features of the response to antidepressant treatment
Short term trials of antidepressants (4-12 weeks). 50-60% respond to therapy, 30% respond to placebo. 40% enter remission. 25% given placebo enter remission
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How many patients will not gain adequate response from initial agent?
Half of patients - options for next step (change to another antidepressant from same class/different class, augment with additional agent, combine 2 antidepressants)
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Describe features of changing to same class antidepressant
Assumes depression is homogenous disease, all antidepressants within class are the same/equal efficacy within all types of depression, individuals have identical PK capacity to all antidepressants within a class. STAR*D - greater response to changes
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Describe features of changing to different class antidepressant
Best option. Different pharmacological mechanism of action. If patient was prescribed SSRI, next steps might include - venlafaxine (<150 mg), mirtazapine or TCA. Some different antidepressant classes are less well tolerated than SSRIs
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Describe features of augmentation strategies (1)
If there has been partial response to antidepressant then adding another agent to therapy might boost antidepressant response e.g. buspirone (specific anxiolytic agent, increase NE/dopamine activity, reduce 5HT/ACh activity)
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Describe features of augmentation strategies (2)
Lithium (increase 5HT function). Liothyronine (T3, direct/indirect effects on hypothalamic-pituitary thyroid axis, interface between external emotion/internal CNS biochemistry). Evidence not robust, well tolerated risks do exist
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Describe features of combining antidepressants (1)
More risks (risk for serotonin syndrome - restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death). Last resort option. Most tried combination (venlafaxine or SSRI + mirtazapine)
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Describe features of combining antidepressants (2)
The two distinct pharmacological actions thought to be a combination that maximises neurotransmitter modulation
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Describe features of STAR*D Programme
Sequenced Treatment Alternatives to Relieve Depression. Focuses on remission, met DSMIV criteria for major depression. 14 week therapy. Patients who are not in remission move up a level (<7 points on HAMD 17 rating scale)
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What are the levels for the STAR*D Programme? (1)
L1 (citalopram). L2 (stop citalopram then use either venlafaxine, sertraline or bupropion). L3 (stop therapy, use either mirtazapine or notriptyline or keep current therapy and use lithium to T3 - randomised)
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What are the levels for the STAR*D Programme? (2)
L4 (stop therapy, use tranylcypromine mirtazapine with venlafaxine)
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Describe the results from the STAR*D Programme (1)
Switching therapy - results not statistically different, types of side effect varied with each medicine, burden/rate of side effects not statistically different. Augmenting therapy - bupropion produced greater decline in score than buspirone
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Describe the results from the STAR*D Programme (2)
Not able to tell whether switching or augmentation is the better strategy (not possible to compare due to patients choosing type of treatment)
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Describe the results from the STAR*D Programme (3)
Beyond L2 50% responded to 1st/2nd line treatment. Difficult to treat those in L3/L4 (lower remission rates, neither switching/augmentation was effective at L3). Choice to switch agent made no difference in outcome/tolerability
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Describe the results from the STAR*D Programme (4)
Choice of augmenting agent had no difference in terms of outcome but lithium was associated with greater incidence of side effects compared with T3
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Describe the results from the STAR*D Programme (5)
Treatment outcome (remission), longer times expected to reach remission, clear patient preference (switching/augmenting), patient attrition was substantial
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Describe features of preventing relapse - length of treatment (1)
Single episode of depression treated for 4-6 after symptom recovery. Some patients have 2nd/3rd episode. Meta-analysis of antidepressant - continuing treatment reduces odds of relapse in 1st year, high incidence in first 3 months
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Describe features of preventing relapse - length of treatment (2)
Medication reduces risk of relapse, independent of other risk factors or antidepressant used
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Describe features of dose for prophylaxis (1)
Full dose should be continued for prophylaxis of depression. Single episode treated for 6 months after recovery. Risk of recurrence is high/increases with each episode. Those with multiple episodes may require treatment for years
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Describe features of dose for prophylaxis (2)
Antidepressants are effect, not addictive, not known to lose efficacy over time, not known to cause side new effects with long term use. Medication should discontinue at treatment dose. Antidepressant therapy should be stopped gradually with HCP
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Card 2

Front

Is depression an increasing problem?

Back

Yes - ranked no. 4 in 1990 (Rank of Global Disease Burden - measure in terms of disability adjusted life years). Unipolar major depression estimated to be ranked at no. 2 in 2020

Card 3

Front

Is depression a fatal disorder?

Back

Preview of the front of card 3

Card 4

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What are the links between psychiatric illness and suicide?

Back

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Card 5

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Describe the epidemiology of depression?

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