Major Depression

Stress---> dec. BDNF---> dec. neurogenesis--->Depressive symptoms----->(recycle to stress)

at least 50% reduction in sx

reduction in sx to a level considered "normal" (HAM-D score of no more than 7)

DSM-IV-TR

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)

• Appearance and Attitude toward examiner
• Activity
• Speech and Language
• Mood and Affect
• Thought and Perceptual Disturbances
• Neuropsychiatric Evaluation
• Insight and Judgement

• response
• relapse
• remission
• recovery
• recurrence

loss of interest or pleasure in almost all activities

Just as they are improving and regain energy to plan and carry out a suicide.

Week 1: Anxiety, insomnia


Week 2-3: Loss of energy, Somatic complaints


Several weeks: sleep problems, anhedonia, depressed mood, sexual dysfunction

2 weeks

4-6 weeks at maximum recommended or tolerated dose

4-6 weeks at maximum recommended or tolerated dose.

6-9 months (longer in severely ill pts or those with a history of multiple depressive episodes)

Antidepressants [SSRI, SNRI(TCA's), Bupropion, Mirtazapine]

or

Psychotherapy

• Electroconvulsive therapy
• AD + psychotherapy

AD + AP

Fluoxetine

Paroxetine

• SSRI
• 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)
• MAOI

SSRIs

• NVD
• anorexia
• Wt loss (or gain)
• insomnia
• agitation
• nervousness
• tremor
• akathisia-like syndrome
• HA (frequent)
• sexual dysfunction (any form)
• sweating
• sedation
• W/D symptoms

• 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

• fluoxetine
• paroxetine

• citalopram
• escitalopram

citalopram

• fluoxetine (moderate)
• sertraline (weak)
• paroxetine (weak)

• fluoxetine (Prozac)
• sertraline (Zoloft)
• paroxetine (Paxil)
• citalopram (Celexa)
• escitalopram (Lexapro)

• 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)

• Strong inhibition of 2D6 and 2C9
• Extremely long half-life of parent and metabolite

• Less risk of clinically significant enzyme inhibition than fluoxetine and paroxetine
• Less wt gain than other SSRI's (except fluoxetine)

• Stimulating in some pts (tremor and CNS activation)
• Diarrhea

• 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

• 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

• 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

• Sedating
• 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.

• Don't care about ANYTHING
• dose dependent
• occurs independent of diagnosis
• all SSRI's can cause it

reduce the dose

10 mg/d until 5-10 mg/d final dose is reached, then d/c drug altogether

50 mg/d until final dose of 25-50 mg/d is reached, then d/c drug altogether

• Toxic in OD
• Lots of SE (80% will have 1 or more SE)
• abrupt withdrawal my cause cholinergic rebound (taper over several weeks)

• Amitriptyline (Elavil)
• Imipramine (Tofranil)
• Doxepin (Sinequan)
• Trimipramine (Surmontil)
• Nortiptyline (Pamelor)
• Desipramine (Norpramin)
• Protriptyline (Vivactil)

• Lowering of seizure threshold
• Tremor
• wt gain
• Anticholinergic, Antihistaminic, Alphalytic

• NDRI (mild DA reuptake inhitor) - unique MOA
• No wt gain
• No sexual dysfunction
• Used in combination with SSRI
• Approved for smoking cessation

• 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

• 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

• 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

• SNRI only
• Approved for Depression, diabetic neuropathy, GAD, and Fibromyalgia

• more expensive than Venlafaxine
• Many SE
• 2D6 inhibitor
• avoid in pts with pre-existing liver disease or substantial alcohol use
• NVD
• dry mouth
• insomnia
• anorexia
• constipation

• 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

• significant wt gain and appetite
• significant sedation
• withdrawal symptoms similar to SSRIs

• SRI and 5HT-2 receptor blocker
• Safe in OD
• Minimal anticholinergic SE
• Little effect on cardiac conduction

• dose-limiting sedation
• hypotension
• PRIAPISM (not dose or gender related)

blocks postsynaptic DA receptors (may be useful in pts with psychotic depression)

• Very dangerous in OD (more seizures, coma, ARF, and deaths than other antidepressants)
• Neuroleptic SE d/t MOA

NONE - Blocks reuptake of NE only

• Seizures common
• Possible permanent neurologic sequelae
• Respiratory compromise in OD

• MAOI
• effective for broad range of conditions

• MAOI
• Serious interactions with common foods and drugsWithdrawal rxns
• Hypertensive crisis
• Hypotension
• sedation
• sexual dysfunction
• NMS

• MAOI
• Effective for broad range of conditions

• Serious interactions with common foods and drugs
• Withdrawal rxns
• Hypertensive crisis
• Hypotension
• Stimulant effects (insomnia)
• Sexual dysfunction
• NMS