TRADE NAMES OF ANTIDEPRESSIVES: I. TCAs AMITRIPTYLINE ELEVIL, ENDEP, ETRAFON LIMBITROL, TRIAVIL IMIPRAMINE TOFRANIL DESIPRAMINE NORPRAMIN CLOMIPRAMINE ANAFRANIL NORTRIPTYLENE PAMELOR TRIMIPRAMINE SURMONTIL DOXEPIN ADAPIN, SINEQUAN PROTRIPTYLENE VIVACTIL AMOXAPINE ASENDIN MAPROTILINE LUDIOMIL II. MAOIs ISOCARBOXAZID MARPLAN PHENELZINE NARDIL SELEGILINE ELDEPRYL TRANYLCYPROMINE PARNATE III. SSRIs FLUOXETINE PROZAC SERTRALINE ZOLOFT PAROXETINE PAXIL FLUVOXAMINE LUVOX CITALOPRAM CELEXA IV. NON-TRADITIONAL ANTIDEPRESSANTS: BUPROPION WELLBUTRIN, ZYBAN TRAZODONE, DESYREL NEFAZODONE SERZONE MIRTAZAPINE MIANSERIN, REMERON VENLAFAXINE EFFEXOR BUSPIRONE BUSPARNON-TRADITIONAL ANTIDEPRESSIVES TRAZODONE: Trazodone was quite popular before SSRIs Lacks the antimuscarinic properties of TCAs But has the serotonergic, histaminergic and noradrenergic effects: + Weak but specific serotonin reuptake inhibitor + Is an antagonist at inhibitory serotonin receptors + A metabolite is a 5-HT postsynaptic agonist Hence has fewer side-effects, but is still a potent hypnotic and causes orthostatic hypotension + Often used to treat insomnia + Much less cardiotoxicity than the TCAs + Occasionally causes priapism/enhanced libido + Thus does not have the anorgasmic effects of the SSRIs NEFAZODONE: A second-generation trazodone Has reuptake blocking and 5-HT receptor profile of Trazodone, without the noradrenergic or histaminergic effects Hence is effective against depression with still fewer side effects than trazodone BUPROPION: The MOST nontraditional antidepressant NO direct effect on the serotonin system A relatively specific DOPAMINE reuptake blocker! + also modestly blocks norepi uptake Tends to ACTIVATE not sedate! + also tends to suppress appetite Also effective against ADHD Clinical efficacy against depression equal to standard TCAs and SSRIs SIDE EFFECTS relatively low! + Lower than either TCAs or SSRIs + Can infrequently trigger psychoses + Also infrequently causes seizures + Has no known abuse potential (???) Shouldn't be taken with MAOIs MIRTAZAPINE Has selective à2 antagonist properties in CNS not autonomic system + blockade of à2 receptors on serotonin neurons increases serotonin release Mirtazapine is also a 5-HT2 and 5-HT3 antagonist + Thus increases 5-HT1 neurotransmission Also is a potent histamine antagonist + Hence has antidepressive and sedative properties, not unlike trazodone with few other troubling side effects VENLAFAXINE Blocks 5-HT, NE and (weakly) dopamine reuptake Without effects on receptors Seems to have a rapid-onset antidepressive activity Lacks sedative/hypnotic properties May be efficacious in treating ADHD Side-effects are low, mostly nausea With SSRI-like mild insomnia, activation, appetite depression and of course shouldn't be taken with MAOIs LITHIUM AND BIPOLAR DEPRESSION BIPOLAR DEPRESSION: MANIA IS CHARACTERISTIC OF THIS DISORDER Involves euphoria, excitement, hypersexuality, and inflated self-esteem, little sleep, compulsive partying, spending, gambling + Can sometimes topple over into irritability/ violence + Severe cases of mania sometimes involve schiziform thought disorders UNIPOLAR MANIA ALSO SEEN PATIENTS IN MANIC PHASES ARE RESISTANT TO TREATMENT - HAVING TOO MUCH FUN! BIPOLAR DISORDERS HAVE A HIGH GENETIC COMPONENT LITHIUM SALTS IN TREATMENT OF BIPOLAR DISORDERS Lithium can both halt manic episodes AND prophylact- ically reduce the mood swings characteristic of bipolar disorder As usual, takes several weeks to achieve full effect DISCOVERY: In 1949, John Cade (MD in Bundoora, Australia, superintendent of a mental asylum there) found that lithium salts made guinea pigs dopey + Cade gave lithium to manic patients, with excellent results + Publishes results in an obscure Australian medical weekly 1952 - Mogens Schou, young Danish researcher, replicates Cade's findings Not approved by FDA until 1970 - and then only after psychiatrists threatened civil disobedience + Without drug company money, 21 years elapsed between discovery and usage! Mechanism(s) - Not a clue, this ion alters just about every known neurotransmitter system! LITHIUM SIDE-EFFECTS: SIDE EFFECT PERCENT EXPERIENCING RANK ORDER IN NONCOMPLIANCE EXCESSIVE THIRST 35.9 POLYURIA 30.4 4 MEMORY PROBLEMS 28.2 1 TREMOR 26.6 3 WEIGHT GAIN 18.9 2 DROWSINESS 12.4 5 DIARRHEA 8.7 ANY COMPLAINT 73.8 NO COMPLAINTS 26.2 OTHER TREATMENTS: Severe mania doesn't respond to lithium, requires neuroleptics OBSESSIVE-COMPULSIVE DISORDER EPIDEMIOLOGY: 2.5 % lifetime, 1.6 % annual incidence in USA No sex difference Often starts in childhood Usual genetic predisposition + Often appears with depression or phobia + Also family members have a high risk for Tourette's syndrome SYMPTOMS: OBSESSIONS: Intrusive, inappropriate, recurring thoughts, often frightening or disturbing: + Contamination - 55% + Aggressive thoughts - 50% + Need for Symmetry - 37% + Somatic concerns - 35 % + Sexual content - 32% COMPULSIONS: Ritualistic, repetitive behaviors linked somehow to the obsessions + Cleaning + Checking + Counting + Ordering/arranging + Hoarding/collecting These symptoms must be disruptive of normal functioning AND unlike schizophrenia, victims MUST be at least partially aware of the bizarre and inappropriate nature of their obsessive thoughts and compulsive rituals CAUSES: Linked to abnormal activity in orbitofrontal cortex and underlying regions of the striatum TREATMENT: Clomipramine and SSRIs are at best modestly effective About 40% of patients respond And therapeutic effects take up to 12 weeks! Psychosurgery is reportedly effective (??) BIOLOGICAL BASES OF DEPRESSION ENDOCRINE ABNORMALITIES IN DEPRESSION: HYPOTHALAMIC - PITUITARY - ADRENAL HYPERACTIVITY: A quick review: hypothalamus CRF Pituitary ACTH, endorphins Adrenals Cortisol release Dexamethasone suppression test: About half of depressives DON'T suppress cortisol secretion after dex administration. CRF elevated in depressives and suicides ACTH, endorphin response to CRF blunted Diminished hippocampal volume Pituitary gland enlargement Adrenal enlargement Increased ACTH, cortisol production BUT: is all this CAUSE or EFFECT? HYPOTHALAMIC - PITUITARY - THYROID HYPO- ACTIVITY Quick review: Hypothalamus thyrotropin-releasing hormone (TRH) pituitary TSH thyroid T3, T4 release TRH, T3 receptors in brain Hypothyroidism often accompanied by depression Some depressives respond to thyroid treatment