Depression Flashcards
Name the drugs that are classified as irreversible monoamine oxidase inhibitor MAOIs
Phenelzine
Tranylcypromine
Iproniazid
isocarboxazid
MAO can regulate intraneuronal concentration of NA/5HT, there are two types of MAO… their substrates are…
where are MAO expressed
MAOA- substrate preference 5HT
MAOB- substrates preference DA
WIDELY expressed in nerve terminals and gut wall (it inactivates ingested amines)
What amines is rich in cheese?
Tyramine (sympathetic amine)
What is the effect of tyramine when a non selective MAOI is used?
Tyramine is an amine. when MAOi is used-
NOT metabolised by gut but absorbed to blood - sympathetic NT effect
E.g. Hypertension, headache, angina, cardiac arrest, pulmonary oedema
Side effect of MAOIs
- hypotension (no NA)
- atropine like effects e.g. Dry mouth, constipation, blurred vision, difficulty in micturition (cant see, cant pee, cant spit, cant shit)
- hepatocellular jaundice (MAO in gut and liver)
Name a drug under reversible inhibitor of MAOA (RIMA)
Moclobemide
What’s the benefit of RIMA over MAOI?
Allow MAOA inhibition to be partially OVERCOME by high conc of sub e.g. Tyramine
- no cheese (sym) reaction
Name 4 drugs under tricyclic antidepressants (TCA) inc one rcomd by NICE
Nice: lofepramine
Amitriptyline
Imipramine
Clomipramine
What’s the MOA of TCAs
Characteristics of action
Competitive Sub for anime reuptake transporter
Block reuptake by nerve terminals
Non selective so blocking mAChR/ 5HT ->SE
Major metabolite is active so long duration of action
Name 4 SSRI
Fluoxetine Prozac
Paroxetine
Citalopram
Escitalopram (active part of citalopram)
What’s the biological / emotional component of depression sensitive to
Bio: antidepressants effect on NA
AD effect on 5-HT
SSRI can be used to treat….
Depression and anxiety disorders
SSRI vs TCA
- Better SE profile
Safe in overdose
Same efficacy
Same onset of action
What’s venlafaxine
PK profile
Serotonin and NA uptake inhibitor
- greater efficacy
- lower se
- more rapid onset
Name a NA and dopamine uptake inhibitor
Bupropion
Name 4 MA receptor antagonist
- mirtazapine block a2 R and 5HT R More release of NA/5HT - Trazodone block 5HT R and 5HT reuptake - mianserin block many 5HT R, a1/2 R - agomelatine block melatonin R (sleep inducing chemical) useful in depression with sleep disturbance
What is the monoamine hypothesis
Depression is a function of deficit of 5HT and/or NA in the brain
What are the limitations of antidepressants
1 efficacy: low. <40% achieve remission from Symptoms
2 tolerability: s/e, SSRI-emotional blunting
3 time of onset: 4-6w= long!
4 safety of AD : risk of suicide on overdose
Contradiction b/w monoamine theory and AD
Antidepressant blocks 5TH uptake as soon as the drug is used however the onset of action takes 4 weeks-> chronic adaptive changes in response to antidepressant rather than acute effect of blocking the transporter that gives the response
chronic trts are needed even tho 5HT reuptake is blocked asa D is used
List the types of meds for bipolar disorder
1st line: lithium (80% of relief but li toxicity!)
Anticonvulsant: carbamazepine, valproate, lamotrigine
Antipsychotics: olanzapine, risperidone, quietiapine, aripiprazole
Describe the clinical utility of lithium
and pk
- Mainly used prophylactically
- reduce mania in acute episodes, reduce depression and manic phases
- LONG-TERM treatment (2y) to prevent relapse
- 3-4w onset of action - Narrow therapeutic window 0.4-1 mmol/L
- Potentially fatal > 1.5 mmol/L
- Frequent conc monitoring required
- Damage kidneys
what are the Criteria for Manic and Hypomanic Episodes
Elevated mood PLUS 3 of the following: - loss of sleep - agitation - excessive talking - flights of ideas - inflated self-esteem - psychomotor agitation, goal directed behavoir - easily ditractable - excessive involvement in pleasurable activties with negative consequences: shopping For manic episode: - Symptoms last for 1 week OR require hospitalization - cause functional impairment For hypomanic episode: - Symptoms last at least 4 days - impairment is not marked
what are the criteria for dysthymic disorder
Chronic depression – Depressed mood for at least 2 years (not severe enough for a MD episode) PLUS 2 other symptoms: - Poor appetite or overeating - Sleeping too much or too little - Psychomotor agitation or retardation - Loss of energy - Feelings of worthlessness - Difficulty concentrating or indecisiveness - Recurrent thoughts of death or suicide
three features of Major Depressive Disorder (MDD)
- episodic
- recurrent
- subclinical depression (not meeting the criteria but causing functional impairment)
sadness plue 3 sym for 10 days
what scale does Clinician use to assess MMD?
Hamilton Depression Rating Scale (HAM-D or HDRS)
Montgomery-Asberg Depression Rating Scale (MADRS)
what is the Self-rating assessment scales called
Beck Depression Inventory (BDI)
what is the DSM 4 criteria for MMD?
low mood everyday OR anhedonia (loss interest in doing things) puls 4 of the sym
- loss, oversleep
- weight gain/loss
- psychomotor agitation/ retardation
- fatigue everyday
- worthlessness/guilt
- lack of concentration
- thought of suicide
classify unipolar depression
what are the trt options like
- reactive depression 75% caused by stressful event in life, temporary
- endogenous depresion 25%, run in the family
same trt for both
what is the HDRS17 score for normal and for moderate depression
A score of 0-7 is “normal”
A score of >20 indicates moderate severity and required for entering a clinical trial
what is cyclothymic disorder
bipolar disorder
Milder, chronic form of bipolar disorder
Lasts 2 years
periods with hypomanic and mild depressive symptoms
what are the further subtype of depression?
- Seasonal (SAD)
Episodes happen regularly at a particular time of year - Rapid cycling (Bipolar I and II)
- Postpartum onset: Within 4 weeks of giving birth
- Catatonic (physical) features: Extreme physical immobility or excessive peculiar physical movement
- Psychotic features: Delusions or hallucinations
- Melancholic: Inability to experience pleasure (anhedonia)
what is the monoamine hypothesis of depression and of mania
- depression: low level of 5HT and NA and DA
- mania: high level of NA and DA but LOW level of 5HT
what is the effect of reserpine and triptophan depletion
bock vMAT, inhibits NA and 5TH storage- depression
reduce 5HT synthesis, induce relapse
3 Psychological treatment of mood disorders
- interpersonal psychotherapy (IPT)
short term, focus on current relationships - cognitive therapy
monitor and identify automatic thoughts, replace -ve thoughts with natural thoughts, behavioral activation - MBCT mindfulness based congnitive therapy
meditation to prevent relapse
what are the pharm effects of MAOI, TCA, SSRI
MAOIs increase 5-HT, NA by inhibiting metabolism
TCAs increase 5-HT, NA by blocking reuptake
SSRIs increase 5-HT by blocking reuptake
what are the long term s/e of li
Thyroid goitre
Nephrotoxicity
Hair loss
what is the depression rating scale that is used in the UK / in the USA
UK: ICD-10 international classification of disease (from WHO)
USA: DSM-V (more focused on psychological instead of somatic effects of depression)
name Medicines that are Precipitating Depression
Corticosteroids Oral contraceptives H2 receptor antagonists Calcium channel blockers Retinoic acid derivatives Interferon & ribivarin preparations Methyldopa
what are the treatment goals for depression
- increase remission
- reduce relapses
- restore physical and social function
what is advance directives and when should you consider pt to carry this out?
pass the right over trts to a family member when the pt has lost mental capacity to make decisions. Consider advance directives, especially for people who have recurrent severe or psychotic depressions, and for those who have been treated under the Mental Health Act.
trt options for mild depression
SOCIAL INTERVENTION: Educate, Sleeping routine, anxiety/ stress management, regular Exercise, Guided self-help (books and leaflets), general advice eg financial. Social contact e.g.
Support groups. Mindfulness, meditation, yoga, aromatherapy
Psychological interventions:CBT
trt options for moderate to severe depression
SOCIAL INTERVENTION
Psychological interventions: CBT, Problem solving, Interpersonal psychotherapy IPT
Pharmacological interventions: ECT
what factors need to be considered before rx antidepressant?
- Previous response to an antidepressant
- increased bleeding risk w SSRI and aspirin or nsaid
- Older pt or medical illness – use citalopram, sertraline or AD w less anticholinergic cv risk
- avoid fluoxetine, paroxrtine (long t1/2 more interactions)
- toxicity in overdose in pt w Suicidal risk – avoid TCA’s exc lofepramine
- Insomniac – pick one w sedative SE, but warn about drowsiness and driving risks (mirtazapine)
- Still drinking – citalopram or sertraline
what are the s/e of ssri
does all ssri have similar s/e profile
does all ssri have same duration of actions
what is it like comparing to TCA
yes All ssris have similar side effect profile: GI disturbance/ bleed (x NSAID or aspirin), sexual dysfunction May increase anxiety and/or suicide ideation initially agitation, insomnia More rarely hyponatraemia Withdrawal syndrome avoid alcohol Different duration of actions Safer in overdose than TCA
Serotonin Syndrome
- cause
- onset
- symptoms
- two or more agents increasing levels of serotonin are co-prescribed.
- rapid onset (within minutes)
- triad of sym:
cognitive: confusion, agitation, insomnia, hypomania, hypervigilance
autonomic: increase HR,BP->shock, sweating, shivering, high temp40C, N&D, dilated pupil (sympathetic)
somatic: tremor (caused by DA), hyperreflexia, myoclonus, rhabdomyolysis->myoglobin in blood->renal failure
how to trt serotnin syndrome
- STOP SSRI
- Serotonin antagonist cyproheptadine
- Support organ function
- Managing temperature
- Agitation and muscle twitching use BZPs.
s/e of Mirtazapine
- sedation (use at night to help sleep)
- weight gain
caution with MAOI
- Dietary and co-prescription restrictions
What Patients Need to Know about antidepressant
- sym may get worse in first 10 days (suicidal thoughts) but will go away (SSRI)
- takes at least 4 weeks to work
- take for at least 6 m to prevent relapse
- not addictive
- w/d syndrome on sudden cessation
- interaction w otc (st.john wort)
what are the w/d syndromes
how to avoid
FINISH
F = Flu-like symptoms (fatigue, headache)
I = Insomnia (with vivid dreams or nightmares)
N = Nausea (sometimes vomiting)
I = Imbalance (dizziness, lightheadedness)
S = Sensory disturbances (visual, “shock-like” sensations)
H = Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness)
- w/d over 4 w, reduce dose in stepwise
T or F: 1 in 10 ppl suffer depression at some point in their life
F: 1 in 4 ppl
risks factors of depression
- genetic (25% familiar unipolar disorder)
- anxiety
- lack of parental care
- gender
- insomnia
- physical chronic illnesses
- stress
- life event
symptoms of depression
DSM V: sad every day + anhedonia plus 4 of the following - loss or too much sleep - increased or decresed appetite - psychomotor agitation or retardation - feeling of guilt, worthlessness - low self esteem - lack of concentration - low energy, poor memory - recurrent thoughts of suicide also social isolation
Se of SSRI
GI -NV agitation/loss of sleep or sedation Loss of appetite Sexual prob Headache and migraine
