depression & alzheimer's

Depression & Alzheimer's

Depression & Alzheimer's

NAPLEX

p. 109

Antidepressants

Types of depression

• Major depressive disorder, single episode

• Major depressive disorder, recurrent

• Dysthymic disorder

• Dysthymic disorder, not otherwise specified

• Secondary mood disorder due to nonpsychiatric medical condition

Biochemical basis of endogenous depression – reduced / imbalance of NE / 5-HT in CNS

Drug selection/adequate therapeutic trial

Antidepressant Selection FactorsAntidepressant Selection Factors

Patient factors Age, comorbid conditions, medication profile,

preference, previous successes and failures of specific agents

Other factors Cost, convenience, adverse-effect profile,

safety Typical response rate: 4 to 6 weeks Adequate trail is 6 month on effective dose

Patient factors Age, comorbid conditions, medication profile,

preference, previous successes and failures of specific agents

Other factors Cost, convenience, adverse-effect profile,

safety Typical response rate: 4 to 6 weeks Adequate trail is 6 month on effective dose

Antidepressants (cont’d)

Common Adverse Effects by Receptor Subtype

H-1 receptor blockade:

Sedation, drowsiness, weight gain

Acetylcholine blockade:

dry mouth, blurred vision, tachycardia, constipation, urinary retention, memory impairment

Norepinephrine blockade:

Tremors, jitteriness, tachycardia, diaphoresis, HTN, erectile dysfunction

5-HT blockade:

sexual dysfunction, N/V/D, anorexia, anxiety, asthenia, insomnia, EPS


Common Adverse Effects by Receptor Subtype

5-HT2 blockade:

sexual dysfunction, hypotension

Alpha-1 blockade:

orthostasis, drowsiness

Alpha-2 blockade:

priapism

Withdrawal syndrome:

Flu-like syndromes, dizziness, adverse GI effects, paresthesias, mood, appetite, and sleep changes

Agent Dosing Kinetics and Pharmacology Side Effects

Tertiary - TCAs

Amitriptyline(Elavil)

Initial Dosing: 25 - 50 mg HSMaintenance: 150-200mg / dayChronic pain: 25 -100mg / dayMax: 300 mg/day

98% PBt1/2: 24 hoursMetabolized via 1A2 and 2D6active metabolite: nortriptylineBL: >100 ng/ml (amit+nort)

Common Side Effects:Orthostatic HypotensionAntihistaminergicAnticholinergicAntiadrenergicPhotosensitivitySexual DysfunctionSIADHSwitching (depression to mania)

Imipramine(Tofranil)

Initial Dosing: 25 - 50 mg HS(lower for panic)Maintenance: 150-200mg / dayMax: 300 mg/day

98% PBt1/2: 24 hoursMetabolized via 1A2 and 2D6active metabolite: imipramineBL: >200 ng/ml (imip+ desip)

Doxepin(Sinequan)

Initial Dosing: 25 - 50 mg HSMaintenance: 150-200mg / dayMax: 300 mg/day

98% PBt1/2: 24 hoursactive metaboliteMetabolized via 1A2 and 2D6

Clomipramine(Anafranil)

Initial Dosing: 25 - 50 mg HS(lower for panic)Maintenance: 150-200mg / dayHigher for OCD * only TCA effective

for OCDMax: 250 mg/day (incr. Risk of

seizures)

98% PBt1/2: 36 hoursactive metabolite: n-desmethyl

clomipramine (t1/2: 52 hours)Metabolized via 1A2, 2D6Clomip: 5HTNDClomip: NE

Secondary TCAs

Nortriptyline(Pamelor)

Initial dose: 25 - 50 mgMaintenance: 100-125mg / dayMax: 150mg/day

98% PBt1/2: 24 hoursMetabolized via 2D6BL: 50-150 ng/mlTwice as potent as other TCAs

side effects same as above but less severe

Nortriptyline: least orthostaticDesipramine: least

anticholinergic and least weight gain

Desipramine(Norpramin)

Initial dose: 25 - 50 mg HSMaintenance: 150-200mg/dayMax: 300 mg/day

98% PBt1/2: 24 hoursmetabolized via 2D6BL: >100 ng/ml

Medication Dosing Guidelines Kinetic Parameters / Pharmacology

Side Effects

Nefazodone(Serzone)

Di: 25mg BIDDm: 300-500mgMax: 600mg/d

Inhib: 3A4Act. Metab: m-CPPt1/2: 12 hrs - inhibition of own metabolism

allows for Q Day dosing (Cpss reached am day 5)

Hepatotoxicity – Discontinued!

Same serotonin receptor stimulation profile with some mild inhibition of norepinephrine reuptake blockade, blocks 5HT2, therefore: see less anxiety, insomnia, and akathisia

Sedation may occurLittle to no sexual dysfunction. No priapism.Photosensitivity and SwitchingHepatotoxicity - Discontinued

Venlafaxine(Effexor)

Di:25mg BIDDm: 225-350mgMax:375mg/dSA allows for once daily

dosing.

40-50%PBNo InhibitionAct. Metab:O-D-venlafaxinet1/2: 12 hrs (Cpss am day 4)MOA: Low dose sertonergic, Moderate doses

adds noradrenergic, at high doses dopaminergic activity added

Stimulates all serotonin receptorsNoradrenergic stimulation, DA side effects possible

but uncommon, Photosensitivity and Switching can occur

Dose dependent hypertension (>375mg/day) very patient variable

Mirtazapine(Remeron)

Di: 15mgDm: 30-45Max: 60mg

t1/2: 24hrs (Cpss am day 5)no inhibition

Not associated with GI side effects of SSRIsSedation and weight gain most common, at higher

doses may be more stimulatingPhotosensitivity and Switching can occurLittle to no sexual dysfunction

Bupropion(Wellbutrin)

Di: 75mg BIDDm:150mg BID SRMax:450mg/dMax one time

dose=150mg reg rel.

Not for panicSR does NOT allow for

once a day dosing

Active and Inactive metabolitest1/2: 12hrs (Cpss am of day4)MOA: Increases levels of norepinephrine and

dopamine

Overstimulation, headache, insomnia, nausea, agitation

High doses may cause psychotic symptomsLittle to no sexual dysfunctionPhotosensitivity and Switching (less?)Contraindicated in seizure disorder.

Medication Dosing Guidelines Kinetics and Pharmacology Side Effects

Fluoxetine(Prozac)

Inital dose: 10 - 20 mg a day (2.5 mg for panic)

For depression and panic: 10 - 20 mg

For OCD: higher maintenance doses required

94% PBT1/2: 1-3 days (parent)active metabolite: norfluoxetine (t1/2: 7-10 days)Inhibits 2D6 and 3A4PG use considered safe, especially 2nd and 3rd

trimesters

Side effects: Non-selective activation of serotonin receptors by increased serotonin.

Receptor Stimulation5HT1A Antidepressant

Anti-obsessional Antipanic / antisocial

phobia, Anti-bulimia5HT1D Antimigrane5HT2 Anxiety, Akathisia,

Agitation, Insomnia, Panic attacks, Sexual Dysfunction

Blockade at the receptor antagonizes these actions

5HT3 Nausea, GI distress, Diarrhea, Headache

Blockade at this receptor antagonizes these actions

Most stimulating: Prozac > Zoloft > Celexa > Paxil > Luvox

Most diarrhea: Zolft > Paxil > Prozac > Celexa > Luvox

All cause photosensitivity and switching (from depression to mania), Hyponatremia

Fluvoxamine(Luvox)

Initial dose: 25mg BID(smaller for panic)Maintenance for

depression: 200mg

for OCD higher

77% PBT1/2: 12 hoursNo active metabolitesInhibits 1A2, 2C, 3A4, 2D6

Sertraline(Zoloft)

Initial dose: 50mg HS(smaller for panic)Maintenance for

depression: 150mg

for OCD higher

95% PBactive metabolite (N-desmethylsertraline)T1/2: 24 hoursInhibits: 2D6 (mild)PG use - initial reports indicate safety

Paroxetine(Paxil)

Initial dose: 10 - 20 mg a day (smaller for panic)

Maintenance for depression: 40mg

for OCD higher

95% PBT1/2: 24 hoursNo active metabolitePG use - initial reports indicate safety

Citalopram(Celexa)Escitalopram(Lexapro)- L isomer,

Initial dose: 10- 20 mg a day (smaller for panic)

Maintenance for depression: 40mg

for OCD higher

80% PBT1/2: 24 hoursMetabolites less active than parent compoundSlight Inhibition of 1A2, 2D6, 2C19Substrate for 3A4 (parent) and 2C19 (metab)PG: Category C, use not recommended at this time

due to lack of information

Trazodone(Deseryl)

Initial dose: 25 mg a day Primary use: SLEEPMaintenance forsleep: 50 - 150mg HS(150mg MAX)Depression: 400mg/d

93% PBActive metabolite (m-CPP)T1/2: 12 hoursProserotonergic - not an SSRI

High alpha-adrenergic blockade results in high incidence of orthostatic hypotension

Very SedatingPriapism - rare, urologic emergency


Monoamine Oxidase (MAO) Inhibitors

- effective in refractory depression

Isocarboxazid (Marplan)

Phenelzine sulfate (Nardil)

Tranylcypromine sulfate (Parnate)


Substances to be avoided when using MAO inhibitors

Food with Tyramine Content

• Aged cheeses

• Sauerkraut

• Smoked aged, or pickled meat or fish

• Yeast extracts

• Fava beans

• Beer, red wine

• Avocados

• Meat extracts


Substances to be avoided when using MAO inhibitors (cont’d)

Medications

• Phenylpropanolamine

• Pseudoephedrine

• Meperidine (Demerol)

• Methyldopa (Aldomet)

• Morphine

• Reserpine

Alzheimer's DrugsAlzheimer's Drugs

NAPLEX

p. 118

Drugs for Alzheimer’s Disease

Cholinesterase inhibitors: all enhance cholinergic activity• Donepezil (Aricept)• Galantamine (Razadyne) (Reminyl – D/C))• Rivastigmine (Exelon)

- Exelon patch approved 7-2007

Glutamate antagonists• Memantine (Namenda)

Miscellaneous agents• Vitamin E• Selegiline (Eldepryl)

Cholinesterase Inhibitors DosingCholinesterase Inhibitors Dosing

Drug Starting dose

Time before Increasing dose

Increase dose by

Max dose

Donepezil (Aricept)

5mg QHS 6 weeks 5mg QHS 10mg QHS

Rivastigmine (Exelon)

1.5mg BID 2 weeks 1.5mg BID

6mg BID

Galantamine (Razadyne)

4mg BID 4 weeks 4mg BID Recommen-ded range of 16-24 mg a day.

• Dose dependent side effects require titration• Start low and take in steps to avoid side effects

Drugs for Alzheimer’s Disease

Adverse Effects

Cholinesterase inhibitors:• Hepatotoxicity• Cholinergic effects (N/D, anorexia, salivation)• Bradycardia• Headache

Glutamate antagonists• Hypertension• Tachycardia• Insomnia

A prescription is presented for galatamine (Razadyne). The patient is most likely being treated for:

A) Alzheimer'sB) Nocturnal enuresisC) Manic-depressive illnessD) ADHDE) Insomnia

A prescription is presented for galatamine (Razadyne). The patient is most likely being treated for:


A prescription is presented for galatamine (Reminyl). The patient is most likely being treated for:


A prescription is presented for galatamine (Reminyl). The patient is most likely being treated for:


Orthostatic hypotension is characterized by which of the following symptoms?

A. Peripheral vasoconstriction

B. Increased urination

C. Urinary retention

D. Dizziness

E. Dry mouth

Orthostatic hypotension is characterized by which of the following symptoms?

A. Peripheral vasoconstriction

B. Increased urination

C. Urinary retention

D. Dizziness

E. Dry mouth

Which SSRI(s) is not required to be tapered when discontinued?

I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)

A) I onlyB) III onlyC) I & II onlyD) II & III onlyE) I, II, III

Which SSRI(s) is not required to be tapered when discontinued?

I Fluoxetine (Prozac)II Paroxetine (Paxil)III Sertaline (Zoloft)


How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months


How long is an adequate continuation of an antidepressant before considering a different agent?I. 4 weeksII. 2 monthsIII. 6 months


What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day


What is considered an optimal augmentation approach to someone not responding to SSRI therapy?I Add Lithium 600mg BIDII Add Cytomel 25mcg/dayIII Add Bupropion 150mg/day


Good Luck!Good Luck!

You will all do great!You will all do great!

depression & alzheimer's

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