L09-L10 Depression Flashcards
Pharmacological & psychological treatments should be 1st-line Tx in cases of mild depression. True or false?
False!
Psychosocial Tx ALONE should be the 1st-line Tx for MILD depression.
Pharmacological Tx is added on as mainstay Tx for moderate & severe depression.
Among persons with a mental illness, it is unlikely that they too have a chronic physical illness. True or false?
False.
Among persons with a mental illness, 50.6% also have a chronic physical illness.
Which psychiatric conditions significantly increase the risk of early mortality?
Schizophrenia, major depression & alcohol-use disorders.
- For each completed suicide, there were 7 unsuccessful attempts.
Which independent predictors are used to detemine the suicidality risk in psychiatric patients?
1) Hx of attempted suicide using highly lethal means
2) Coexisting significant physical illness
3) Delusions
What is the clinical presentation of a psychiatric patient diagnosed with major depressive disorder (MDD)?
ALL three criteria MUST be fulfilled:
1) At least 5 symptoms of In SAD CAGES present during the same 2-week period representing change from previous functioning WITH either (a) depressed mood or (b) loss of interest
In SAD CAGES:
- Interest (decreased; anhedonia)
- Sleep (insomnia/hypersomnia), Appetite (decreased; weight loss), Depressed (irritable in children)
- Concentration (impaired decision making), Activity (psychomotor retardation/agitation), Guilt (worthlessness), Energy (fatigue) & Suicidality
2) Significant distress or impairment in social, occupational or other impt areas of functioning
3) NOT caused by underlying medical condition or substance
Antidepressants are appropriately indicated as first-line Tx for patients diagnosed with bipolar affective disorder. True or false?
False!!
AVOID antidepressants due to immediate mood swings to mania, which exacerbates the condition!
Antidepressants are appropriately indicated as first-line Tx for patients diagnosed with adjustment disorder with depressed mood. True or false?
False!
Adjustment disorders are NOT indicated for pharmacological Tx.
Non-pharmacological approaches preferred since etiology is NOT biological in nature!
- Smx occur w/in 3 months of onset of a stressor, BUT once stressor is terminated, smx do NOT persist for additional 6 months.
What are two important screening questions to ask psychiatric patients in determining their suitability to antidepressant Tx?
1) Any Hx of manic/hypomanic episodes?
- Antidepressants may cause “manic switch” in pt. w/ underlying bipolar disorder.
2) Any suicidal/homicidal ideations & risks?
- Conduct mental state exam (MSE) for accurate diagnosis, including suicidality risk!
- If yes, likely need antidepressants.
What lab parameters should be investigated to exclude other differential diagnoses from MDD?
- Vitals, weight & BMI
- FBC (WBC in particular for infections e.g. meningitis/encephalitis)
- Renal panel: Urea, electrolyte, creatinine
- LFTs
- TFTs (thyroid) for hypothyroidism
- ECG for CV risk
- Folate & Vit B12 for anemia
- Fasting blood glucose for hypoglycemia & diabetes
- Lipid panel for CV risk
- Urine toxicology for substance misuse & pregnancy
Depression is a diagnosis of EXCLUSION!
What are some of the more common examples of psychiatric rating scales used in clinical settings for depression?
Clinician-rated: Hamilton Rating Scale for Depression (HAM-D)
- Remission = HAM-D score <= 7
- Therapy Goal = smx-free
- Response = 50% improvement
Self-rated: Patient Health Questionaire
- Screening: PHQ-2
- Assessment: PHQ-9
What are some non-pharmacological recommendations to manage patients diagnosed with MDD?
1) Lifestyle/Behavioural Changes
- Sleep hygiene
- Exercise
- Relaxation techniques
2) Psychotherapy
- NOT suitable as monotherapy for moderate & severe depression
- Combine w/ antidepressant for moderate & severe depression
3) Neurostimulation
- Electroconvulsive Treatment (ECT): for severe/refractory cases
- Repetitive Transcranial Magnetic Stimulation (rTMS)
What are some general risk factors that increase the suicidality risk in the general population?
“A poor, elderly, lonely man with physical/mental comorbidities & previous attempts.”
1) Poor socioeconomic status
2) Elderly >= 65 y/o
3) Male gender
4) Presence of physical/mental comorbidities
- esp. major depression, schizophrenia & alcohol-use disorders
5) Hx of suicide attempts/ideations
List some medical disorders which contribute as secondary causes to the diagnosis of depression.
1) Endocrine disorders: Hypothyroidism, Cushing Syndrome, T2DM
2) Cardiovascular: CAD, CHF, MI
3) Deficiency states: Anemia, Wernicke’s encephalopathy
4) Infections: CNS infections, STD/HIV (e.g. neurosyphilis), TB
5) Metabolic disorders: Electrolyte imbalance (hyponatremia & hypokalemia), hepatic encephalopathy
6) Malignancy
7) Neurological: Alzheimer’s disease, epilepsy, pain, Parkinson’s disease, post-stroke
Under what conditions should PHQ-9 be considered to screen for possible depression?
Positive response to either question of PHQ-2:
Over the past two weeks, how often have you been bothered by any of the following problems?
1) Little interest or pleasure in doing things
2) Feeling down, depressed or hopeless
A negative response to both questions is considered a “negative” result for depression screening.
Which classes of drugs are clinically used as first-line antidepressant monotherapy today?
EQUIVOCAL efficacy between these four classes:
SSRIs, SNRIs, Mirtazapine (NaSSA) & Bupropion (NDRI)
- Select based on target smx, comorbidities, DDI, prior response & preference (i.e. sexual dysfunction of SSRIs & SNRIs)
However, if cost is a factor:
SSRIs, SNRIs, Mirtazapine (NaSSA) & Bupropion (NDRI)
- First three drug classes are heavily subsidised by MOH
- Bupropion, while first-line under CPG, isn’t subsidised by MOH.
Explain the different phases of antidepressant Tx.
1) Acute Phase Tx:
- Adequate trial = adequate dose (i.e. lowest effective dose) + adequate duration
- Duration = 4-8 weeks, max. 12 weeks
- Pt. may get anxious & jittery upon 1st exposure
- Certain elderly pt. may take more time to respond
- Delayed onset due to downregulation of presynaptic autoreceptors (i.e. reuptake receptors)
- Physical smx (e.g. sleep & appetite) may improve in 1-2 weeks
- Mood smx take longer to improve i.e. 4-6 weeks
2) Continuation Phase:
- 1st episode of MDD: Continue for at least 4-9 months after acute-phase Tx
- i.e. TOTAL duration = at least 6-12 months = initiation + acute phase + continuation phase
3) Longer-Term Maintenance Therapy:
- Consider if high risk, at least 2 MDD episodes & geriatric MDD
- Maintain trial dose if no serious side effects reported thus far
Explain why the onset of first-line antidepressants in improving the mood symptoms associated with depression is delayed.
- Inhibition of serotonin uptake results in increased levels of 5-HT w/in synaptic cleft
- Presynaptic autoreceptors regulating synthesis & release of 5-HT keep receiving signals due to increased levels of 5-HT w/in synaptic cleft
- Led to downregulation of presynaptic autoreceptors & thus less negative feedback in regulating 5-HT neurotransmission
- Time is required to built tolerance & revert to original levels of expression of presynaptic autoreceptors
- Thus, longer onset of antidepressants
Explain the steps of chemical neurotransmission.
- Precursors are transported from blood into the brain.
- Subsequently converted into neurotransmitters via enzymatic processes & stored in synaptic vesicles.
- Neurotransmitters are released into synaptic cleft, where they either interact with:
(a) presynaptic autoreceptors to regulate synthesis & release, or
(b) postsynaptic receptors to induce events of downstream signal transduction cascade.
List all clinically available antidepressant classes in SG.
First-line antidepressant monotherapy:
1) SSRIs (serotonin selective reuptake inhibitors)
2) SNRIs (serotonin-norepinephrine reuptake inhibitors)
3) NaSSA (noradrenaline & specific serotonin antidepressants)
4) NDRIs (norepinephrine-dopamine receptor inhibitors)
Alternative:
1) TCAs (tricyclic antidepressants)
2) RIMAs (reversible inhibitors of monoamine oxidase i.e. MAO-A selective inhibitors)
3) SMSs (serotonin modulators & stimulators)
4) Melatonin receptor antagonists
5) SARI (serotonin antagonist & reuptake inhibitor)
Name a few examples of SSRIs used clinically.
Drug -> Active metabolite:
1) Fluoxetine -> Norfluoxetine
2) Fluvoxamine
3) Escitalopram / Citalopram
4) Sertraline
5) Paroxetine
Name a few examples of SNRIs used clinically.
Drug -> Active metabolite:
1) Venlafaxine -> Desvenlafaxine
2) Duloxetine
Name an example of NaSSA used clinically.
Mirtazapine
Name an example of NDRI used clinically.
Bupropion
Name a few examples of TCAs used clinically as an alternative to first-line antidepressant monotherapy.
Drug -> Active metabolite:
1) Amitriptyline -> Nortriptyline
2) Imipramine -> Desipramine
3) Dothiepin (Dosulepin)
4) Clomipramine (more for OCD)
Name an example of each alternative drug class (except TCAs) used clinically as an alternative to first-line antidepressant monotherapy.
1) RIMAs: Moclobemide
2) SMSs: Vortioxetine
3) Melatonin receptor antagonists: Agomelatine
4) SARI: Trazodone
Which particular first-line antidepressant is clinically indicated in patients with diabetic neuropathy?
Duloxetine
Aside from being used as a first-line antidepressant monotherapy, what other clinical indications is duloxetine used for?
1) Diabetic neuropathy
2) Stress urinary incontinence
3) Fibromyalgia
4) Chronic musculoskeletal pain
Which antidepressant drug is used for off-label indication of insomnia?
Trazodone
Which SSRI is used for the treatment of bulimia nervosa?
Fluoxetine
Which particular first-line antidepressant is used in the pharmacological treatment of smoking cessation?
Buproprion
Describe the dose-dependent pharmacological effects of venlafaxine.
Low dose: Primarily 5-HT reuptake inhibition
Higher dose: Primarily NA reuptake inhibition
Very high dose: Primarily DA (dopamine) reuptake inhibition
Which SNRI displays a balanced 5-HT & NA reuptake inhibition?
Duloxetine
Which antidepressants have extremely long half-lives as compared to the others (i.e. in days)?
Fluoxetine = 4-6 days w/ chronic dosing Norfluoxetine = 4-16 days Vortioxetine = 66 days
Which SSRI should be taken with food to enhance its bioavailability/absorption?
Sertraline
Which antidepressant is indicated as second-line for obsessive-compulsive disorder (OCD)?
Clomipramine
