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What is the Neurotrophic Hypothesis?
Stress---> dec. BDNF---> dec. neurogenesis--->Depressive symptoms----->(recycle to stress)
What is Response?
at least 50% reduction in sx
What is Remission?
reduction in sx to a level considered "normal" (HAM-D score of no more than 7)
What ist the most widely accepted and most important diagnostic reference used in the care of the mentally ill?
What are the Axes of Multiaxial Classification?
Axis I: Principle psychiatric disorder, developmental disorders, or provisional diagnosis
Axis II: Mental retardation and personality disorders
Axis III: Existing Physical disorders or conditions
- Axis IV: Severity of psychosocial stressors that might have contributed to a new or recurrent
- mental disorder or exacerbation of an existing condition (1 = none 6 = catastrophic)
Axis V: GAF score 1 (persistent danger to self or others) to 90 (minimal or absent symptoms)
What are the parts of a Mental Status Exam (MSE)
- Appearance and Attitude toward examiner
- Speech and Language
- Mood and Affect
- Thought and Perceptual Disturbances
- Neuropsychiatric Evaluation
- Insight and Judgement
What are the 5 R's of depression?
What is anhedonia?
loss of interest or pleasure in almost all activities
When are patients at greatest risk of suicide or suicide attempt?
Just as they are improving and regain energy to plan and carry out a suicide.
What is the timeframe for response to depressive symptoms?
Week 1: Anxiety, insomnia
Week 2-3: Loss of energy, Somatic complaints
Several weeks: sleep problems, anhedonia, depressed mood, sexual dysfunction
How long on adequate therapy before a response can be expected in core depressive symptoms?
How long on adequate thereapy before maximum response is seen?
4-6 weeks at maximum recommended or tolerated dose
What is an adequate trial of a drug for depression?
4-6 weeks at maximum recommended or tolerated dose.
How long should therapy be continued after response is seen?
6-9 months (longer in severely ill pts or those with a history of multiple depressive episodes)
What are the TMAP recommendations for therapy in moderate depression?
Antidepressants [SSRI, SNRI(TCA's), Bupropion, Mirtazapine]
What are the TMAP recommendations for severe depression?
- Electroconvulsive therapy
- AD + psychotherapy
What are the TMAP recommendations for severe depression w/psychotic symptoms?
AD + AP
Which drug is the DOC for depression?
Which drug has failed studies in children and should be avoided in absence of compelling reasons to use it?
What drugs are used in the treatment of depression?
- TCAs (SNRI)
- Venlafaxine/desvenlafaxine (SNRI)
- Duloxetine (SNRI)
- Amoxapine (SNRI - basically a TCA)
- Maprotiline (SNRI - basically a TCA)
- Bupropion (NDRI)
- Mirtazapine (NaSSA - mixed NE/5-HT effects)
- Trazadone (SARI - 5-HT antagonist and SSRI)
- Nefazodone (SARI - 5-HT antagonist and SSRI)
What is the class of choice for treatment of depression?
What are the class SE of SSRIs?
- Wt loss (or gain)
- akathisia-like syndrome
- HA (frequent)
- sexual dysfunction (any form)
- W/D symptoms
What are the symptoms of SSRI withdrawal?
- balance problems: dizziness, lightheadedness, vertigo, ataxia
- sensory abnormalities: paresthesias, numbness, electric shock sensations (esp. head, neck, and upper limbs)
- somatic distress: HA, lethargy, sweating, flu-like sx
- sleep disturbances: insomnia, excessive or vivid dreaming
- affective sx: anxiety, agitation, low mood
- GI: NVD, cramps
Which SSRIs have the strongest inhibition of 2D6?
Which SSRIs have the weakest inhibition of 2D6?
Which SSRIs have no known effect on 3A4?
Which SSRIs inhibit 3A4?
- fluoxetine (moderate)
- sertraline (weak)
- paroxetine (weak)
What are the SSRIs used for depression?
- fluoxetine (Prozac)
- sertraline (Zoloft)
- paroxetine (Paxil)
- citalopram (Celexa)
- escitalopram (Lexapro)
What are the advantages of Fluoxetine (Prozac)?
- Extremely long half-life of parent (2-4d) and active metabolite (7-15d) (protects against relapse in intermittently compliant pts, but may be bad if SE are experienced)
- Best evidence for benefit in children and adolescents
- Less weight gain than other SSRI's (except sertraline)
What are the disadvantages of Fluoxetine (Prozac)?
- Strong inhibition of 2D6 and 2C9
- Extremely long half-life of parent and metabolite
What are the advantages of Sertraline (Zoloft)?
- Less risk of clinically significant enzyme inhibition than fluoxetine and paroxetine
- Less wt gain than other SSRI's (except fluoxetine)
What are the disadvantages of Sertraline (Zoloft)?
- Stimulating in some pts (tremor and CNS activation)
What are the advantages of Paroxetine (Paxil)
- Shorter half-life than Fluoxetine (high risk of withdrawal symptoms)
- FDA approved for Generalized Anxiety Disorder (GAD) and Premenstrual Dysphoric Disorder (PMDD)
- (has the MOST FDA approved indications)
- Less activating than fluoxetine and sertraline
What are the disadvantages of Paroxetine (Paxil)?
- Strong 2D6 inhibition
- Increased risk of major congenital malformations (CI in pregnant women!!!!)
- More sedation than other SSRI's
- Most withdrawal issues of SSRI's
- Most anticholinergic effects of SSRI's
- Most sexual dysfunction of SSRI's
- NO use in children
What are the advantages of Citalopram (Celexa)
- Good balance of tolerability, efficacy, and cost (cheapest AD available)
- Generally more sedating than stimulating
- Short half-life, but still able to dose QD
- Weak to no CYP inhibition
What are the disadvantages of Citalopram (Celexa)?
- Reduced clearance in elderly (possibly increase risk of SE)
S-isomer of citalopram
maybe more 2D6 inhibition than Citalopram
NOT FOR DEPRESSION - OCD only in U.S.
What is SSRI-Induced Apathy Syndrome?
- Don't care about ANYTHING
- dose dependent
- occurs independent of diagnosis
- all SSRI's can cause it
How do you manage SSRI-induced Apathy Syndrome?
reduce the dose
How should Paroxetine be tapered?
10 mg/d until 5-10 mg/d final dose is reached, then d/c drug altogether
how should Sertraline be tapered?
50 mg/d until final dose of 25-50 mg/d is reached, then d/c drug altogether
What are the disadvantages of TCAs?
- Toxic in OD
- Lots of SE (80% will have 1 or more SE)
- abrupt withdrawal my cause cholinergic rebound (taper over several weeks)
What are the TCA's used in depression?
- Amitriptyline (Elavil)
- Imipramine (Tofranil)
- Doxepin (Sinequan)
- Trimipramine (Surmontil)
- Nortiptyline (Pamelor)
- Desipramine (Norpramin)
- Protriptyline (Vivactil)
What are the SE associated with TCA's?
- Lowering of seizure threshold
- wt gain
- Anticholinergic, Antihistaminic, Alphalytic
What are the advantages of Bupropion (Wellbutrin)?
- NDRI (mild DA reuptake inhitor) - unique MOA
- No wt gain
- No sexual dysfunction
- Used in combination with SSRI
- Approved for smoking cessation
What are the disadvantages of Bupropion (Wellbutrin?)
- Dose related seizure risk
- Dose limitations: <450 mg/d, <200 mg/dose of SR, <150 mg/dose ofIR
- Rare exacerbation of psychotic symptoms in predisposed pts
What are the advantages of Venlafaxine (Effexor)?
- SNRI (however, dose-dependent for dual action = SSRI at <200 mg/d---------SSRI/NRI at higher doses)
- NO wt gain
- NO Ach, H or alpha adrenergic SE
- Approved for Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD)
- Effective in tx resistant pts???
- Wt loss
What are the disadvantages of Venlafaxine (Effexor)?
- Nausea/vomiting which are more common than with SSRIs (give with meals to avoid)
- Increases diastolic blood pressure
- Sexual dysfunction
- More dangerous than SSRI in OD
- Withdrawal sx
- Wt loss
What are the advantages of Duloxetine (Cymbalta)?
- SNRI only
- Approved for Depression, diabetic neuropathy, GAD, and Fibromyalgia
What are the disadvantages of Duloxetine (Cymbalta)?
- more expensive than Venlafaxine
- Many SE
- 2D6 inhibitor
- avoid in pts with pre-existing liver disease or substantial alcohol use
- dry mouth
What are the advantages of Mirtazapine (Remeron)?
- presynaptic Alpha-2 antagonist (increase 5-HT and NE release)
- Unique pharmacology (good to use in combinations when necessary)
- Little or NO sexual SE
- Not many DI
What are the disadvantages of Mirtazapine (Remeron)?
- significant wt gain and appetite
- significant sedation
- withdrawal symptoms similar to SSRIs
What are the advantages of Trazodone (Desyrel)?
- SRI and 5HT-2 receptor blocker
- Safe in OD
- Minimal anticholinergic SE
- Little effect on cardiac conduction
What are the disadvantages of Trazodone (Desyrel)?
- dose-limiting sedation
- PRIAPISM (not dose or gender related)
What are the advantages of Amoxapine (Asendin)?
blocks postsynaptic DA receptors (may be useful in pts with psychotic depression)
What are the disadvantages of Amoxapine (Asendin)?
- Very dangerous in OD (more seizures, coma, ARF, and deaths than other antidepressants)
- Neuroleptic SE d/t MOA
What are the advantages of Maprotiline (Ludiomil)?
NONE - Blocks reuptake of NE only
What are the disadvantages of Maprotiline (Ludiomil)?
- Seizures common
- Possible permanent neurologic sequelae
- Respiratory compromise in OD
What are the advantages of Phenelzine (Nardil)?
- effective for broad range of conditions
What are the disadvantages of Phenelzine (Nardil)?
- Serious interactions with common foods and drugsWithdrawal rxns
- Hypertensive crisis
- sexual dysfunction
What are the advantages of Tranylcypromine (Parnate)?
- Effective for broad range of conditions
What are the disadvantages of Tranylcypromine (Parnate)?
- Serious interactions with common foods and drugs
- Withdrawal rxns
- Hypertensive crisis
- Stimulant effects (insomnia)
- Sexual dysfunction