ANTIDEPRESSANTS & ANTIDEPRESSANTS & Mood StabilizersMood Stabilizers

Antidepressants

Actions:

Block the reuptake of serotonin and norepinephrine (neurotransmitters) so that more are available in the brain to transmit messages.

Antidepressants

Indications: Recurrent depressive disorders Psychomotor retardation Depression with no clear precipitating event Family history of depression Chronic pain Eneuresis

Antidepressants

Have a long half life and can often be given once a day.

Therapeutic effects of some may not be seen until 3-4 weeks.

Three classifications

SSRIs/ SNRIsTricylcics

Mono-amine Oxidase Inhibitors

A. Selective Serotonin reuptake Inhibitors (SSRIs)

Fluoxetine HCL (Prozac)

Non-tricyclic, less sedation, fewer side effects

Sertraline HCI (Zoloft)

Lower risk of toxicity in overdose, fewer side effects, shorter half-life than prozac

SSRI Antidepressants (cont’d.)

Paroxetine HCI (Paxil):

Effectiveness comparable to Imipramine (Tofranil), shortest half-life, safer for

elderly.

Fluvoxamine (Luvox)

Citalopram (Celexa)

Escitalopram oxalate (Lexapro)

SSRIs Block transport mechanism that

returns unbound serotonin left in synaptic cleft into the presynaptic neuron

Terminates transmission of the message carried by that receptor

When blocked, more serotonin is available to the postsynaptic receptor

A. Serotonin & norepinephrine reuptake inhibitor SNRIs Effexor (Venlafaxine)

Inhibits serotonin & norepinephrine re-uptake

Side effects include: dizziness, migraine, weight gain

Pristiq (Desvenlafaxine) Serzone (Nefazadone) Trazodone HCL (Desyrel)

Norepinephrine-Dopamine Antagonist

Bupropion Hycrochloride (Wellbutrin) Increases norepinephrine and dopamine Provides mild dopamine reuptake Blocks reuptake of norepinephrine Does not affect serotonin reuptake Does not inhibit monoamine oxidase

Side Effects SSRIs and SNRIs Weight gain Impotence and ejaculatory

problems Arousal problems

B. Trycyclic Antidepressants TCAs

Imipramine…….Tofranil

Desipramine……Norpramine, Pertofrane

Amitriptyline……Elavil, Endep

Nortriptyline……Pamelor, Aventyl

Protriptyline……Vivactil

Doxepin…………Sinequan

Trycyclic Antidepressants

Affect norepinephrine, serotonin acetylcholine and histamine receptors

Increase availability of norepinephrine, serotonin

Inhibit transport back into the presynaptic neuron

Side Effects: TCAs

Anticholinergic effects: Common and troublesome in tricyclics: interfere with patient compliance.

dry mouth constipation urinary hesitancy/retention

sweating drowsiness blurred vision

Cardiovascular: Postural hypotension, tachycardia, heart conduction defects.

– TCAs Side Effects

Anticholinergic effects: Closed angle glaucoma worsened Toxic: confusion, psychosis

Other:Weight gain, lowered seizure threshold, EPS

Overdose: 1000 – 4000 mg is fatal

TCAs Side effects

Managing Side Effects of Tricyclic Antidepressants (Cont’d.)If these dangerous side effects occur, advise the patient either to call provider stop the medication, or reduce the dosage.

Orthostatic hypotension Marked, persistent sedation Atropine-like psychosis Cardiovascular conduction defect Seizures Severe anticholinergic effect: urinary retention, etc.

C. Mono-amine Oxidase Inhibitors MAOIs

phenelzine….…………Nardil

isocarboxazide ……….Marplan

tranylcypromine………Parnate

MAO Inhibitors

Actions: Monamine oxidase is an enzyme responsible for destroying epinephrine, norepinephrine and serotonin. MAO inhibitors block this enzyme. The effect is CNS stimulation and increased psychomotor activity.

symptoms relieved in 2-4 weeks

Potential hypertensive crisis it certain foods or medicines ingested

MAOIs

Dietary restrictions necessary: foods high in

tyramine must be avoided: aged cheese, chicken

liver, beer, Chianti wine, cold or sinus medicines,

diet pills, blood pressure regulating meds. Severe

atypical headache is usually the first sign

Side effects: autonomic: orthostatic hypotention,

dizziness, increased appetite anticholinergic effects are

rare.

Other Antidepressant Medications

Psychostimulants

Methylphenidate Hydrochloride (Ritalin)

Dextroamphetamine Sulfate (Dexedrine)

Pemoline (Cylert)

Source: Gomez (1993)

Serotonin Syndrome Occurs when serotonin excitement

occurs A second antidepressant is given

before the first has cleared-need 3 weeks

Overdose of any classification

Serotonin syndrome Altered mental state Fever Tachycardia Tremors High or low blood pressure Clonus

Mood Stablilizers Lithium Antic-convulsants

Lithium Effective in manic excitement and preventative for

manic and depressive recurrences in bipolar 1 patients. Also used in other psychiatric disorders that do not

respond to other drug therapies. Can lead to toxic reactions which may be fatal.

Blood level monitoring is necessary to maintain intherapeutic range.

Therapeutic levels range from .7 to 1.5. Higher levels are used to treat manic or psychotic excitement.

Lithium

Common Indications:Acute ManiaBipolar Prophylaxis

Possibly Effective:BulimiaAlcohol AbuseAggressive BehaviorSchizoaffective disorder

Lithium

Mechanism of ActionUnclear

DosingNarrow therapeutic

indexMonitor blood levels q 2-3 days initially then q 1-3 months levels must be

below 1.5mEq/L

Adverse Effects

Excessive drug

levels

Therapeutic drug

levels

Drug Interactions

Diuretics

Anticholinergic

drugs

LithiumSide effects:Neuromuscular and CNS: tremor (fingers) cog wheeling and mild parkinsonism possible. sluggishness and forgetfulness treated by decreased dose. GI: Chronic nausea, diarrhea, take with food.Weight gain and endocrine effects: Increased appetite and

excessive thirst may cause weight gain - transitory Decreased thyroid levels: Thyroid medication may be necessary.

Renal: polyuria and polydypsia may occur. Dose of drug should be lowered.

LithiumAllergic rashes – may be due to some ingredient in the

capsule. Drug form can be changed to liquid citrate. Cause birth defects

Lithium

Common Causes for Increased Lithium Level:Decreased sodium intakeDiuretic therapyDecreased renal functioningFluid-electrolyte loss (sweating, diarrhea,

dehydration)Medical illnessOverdose

Anti-convulsants– used to promote mood stabilization

Carbamazepine (Tegratol): Used in patients who do not respond to lithium. More effective for rapid-cycling bipolar patients (4 or more affective episodes per year).Blood levels should be monitored weekly for the first eight weeks. Dose should be adjusted to maintain a serum levels of 6-8 mg/L.

Anti convulsants

Side effects: sedation, mal coordination (common) agranulocytosis, aplastic anemia (rare) regular blood counts unnecessary . Watch for fever and sore throat.

Can cause increased liver enzymes but serious hepatic problems rare.

Associated with birth defects.

Anti convulsants

Valproate (Valproic acid) – Depakene, Depakote used in manic and schizoaffective patients (treatment resistant) Improvement occurs in 1-2 weeks. Blood levels should be obtained every few days until 50 mg/l is reached.

Side effects – Major concern – severe hepatotoxicity (may be fatal). Liver function tests should be done every month. Decreased platelet levels can occur.Associated with neural tube birth defects. Very toxic when taken in suicide attempt.

Anti-convulsants Lamitrogine- Lamictal

Anit-convulsant used for type 2 BPD

Side effect- rash, nausea, vomitting and diarrhea.

Other Mood Stabilizers(cont’d.)

Clonazepam (Klonopin) – Benzodiazepine which is useful in treating acute mania

Side effects: sedation, atoxia, disinhibition effect.