AntidepressantsActions:Block the reuptake of serotonin and norepinephrine(neurotransmitters) so that more are available in thebrain to transmit messages.
AntidepressantsIndications: 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/ SNRIs Tricylcics Mono-amine Oxidase Inhibitors
A. Selective Serotonin reuptake Inhibitors (SSRIs)Fluoxetine HCL (Prozac) Non-tricyclic, less sedation, fewer side effectsSertraline 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
Norepinephrine-Dopamine AntagonistBupropion 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 TCAsImipramine…….TofranilDesipramine……Norpramine, PertofraneAmitriptyline……Elavil, EndepNortriptyline……Pamelor, AventylProtriptyline……VivactilDoxepin…………Sinequan
Trycyclic Antidepressants Affect norepinephrine, serotonin acetylcholine and histamine receptors Increase availability of norepinephrine, serotonin Inhibit transport back into the presynaptic neuron
Side Effects: TCAsAnticholinergic effects: Common and troublesomein tricyclics: interfere with patient compliance. dry mouth sweating constipation drowsiness urinary hesitancy/retention blurred vision Cardiovascular: Postural hypotension, tachycardia, heart conduction defects.
– TCAs Side EffectsAnticholinergic effects: Closed angle glaucoma worsened Toxic: confusion, psychosisOther: Weight gain, lowered seizure threshold, EPSOverdose: 1000 – 4000 mg is fatal
TCAs Side effects Managing Side Effects of Tricyclic Antidepressants(Cont’d.)If these dangerous side effects occur, advise the patienteither to call provider stop the medication, or reduce thedosage. Orthostatic hypotension Marked, persistent sedation Atropine-like psychosis Cardiovascular conduction defect Seizures Severe anticholinergic effect: urinary retention, etc.
C. Mono-amine OxidaseInhibitors MAOIsphenelzine….…………Nardilisocarboxazide ……….Marplantranylcypromine………Parnate
MAO InhibitorsActions: Monamine oxidase is an enzyme responsiblefor destroying epinephrine, norepinephrine andserotonin. MAO inhibitors block this enzyme. Theeffect is CNS stimulation and increased psychomotoractivity. 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 signSide effects: autonomic: orthostatic hypotention,dizziness, increased appetite anticholinergic effects arerare.
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 in therapeutic range. Therapeutic levels range from .7 to 1.5. Higher levels are used to treat manic or psychotic excitement.
LithiumMechanism of Action Adverse Effects Unclear Excessive drug levelsDosing Narrow therapeutic Therapeutic drug levels index Drug Interactions Monitor blood levels q 2-3 days initially Diuretics then q 1-3 months Anticholinergic drugs levels must be below 1.5mEq/L
Lithium Side 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 andexcessive thirst may cause weight gain - transitoryDecreased 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
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 convulsantsSide effects: sedation, mal coordination (common)agranulocytosis, aplastic anemia (rare) regularblood counts unnecessary . Watch for fever andsore throat.Can cause increased liver enzymes but serioushepatic problems rare.Associated with birth defects.
Anti convulsantsValproate (Valproic acid) – Depakene, Depakote used inmanic and schizoaffective patients (treatment resistant)Improvement occurs in 1-2 weeks. Blood levels should beobtained every few days until 50 mg/l is reached.Side effects – Major concern – severe hepatotoxicity (maybe 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 isuseful in treating acute maniaSide effects: sedation, atoxia, disinhibition effect.