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39.Depression 3. Therapy.doc

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University of Toronto St. George
Mac Burnham

DEPRESSION 3. Therapy THERAPY FOR MOOD DISORDERS: CHAPTER 25 IN DEPT TEXT, CHAPTER 16 IN CARLSON AN OVERVIEW OF THERAPIES  Antidepressant drugs o work in about 70% of people and takes about a month  ECT o Prolonged temporal-lobe epilepsy schizophrenia and tonic-clonic seizures leading to forced normalization was the motivation for this. Treatment of choice for drug- resistant depressives  TMS o Transcranial magnetic stimulation  Sleep, REM-sleep deprivation  Light therapy (SAD)  Counselling: CBT to improve thinking etc.  Exercise  OTC/Street Drugs: alcohol, THC, stimulants, etc.  Self-medication A HISTORICAL OVERVIEW OF THE DRUGS It all started with anti-histamines. Found it blocked H1 receptor in brain and made you sleepy. Playing with the anti-histamines enabled the advent of chlorpromazine (first antipsychotic). DEPRESSION: ANTIDEPRESSANTS 1) Tricyclic antidepressants (TCAs– Block 5HT and NE reuptake  Came out in the late 1950s.  Work on a lot of people with a 3-4 week delay 2) Monoamine oxidase inhibitors (MAOIs)  Came out in the late 1950s (a tiny bit before the tricyclics)  Probably as effective or more effect than TCAs, but can be very dangerous 3) Second generation antidepressants, etc. (1980s) 4) SSRI’s (1990s) 5) SNRI’s recent (1990s-2000+)  Raise 5HT and noradrenaline together. Don’t know if added NE has benefit MANIA: MOOD STABILIZERS (Antidepressants AS ADJUNCTS) Use antidepressants with care because it can exacerbate mania (which is the more severe) symptom 1) Lithium carbonate (1950s)  This is the mainstay, majority of people respond to it. If they don’t, go onto second line drugs. Not antidepressant or mania. It’s anti-cyclic. Stops the cyclic progression from one mood to the next. 2) Anticonvulsants (recent)  Several anticonvulsants used for atypical (resists lithium) bipolar.  Use valproate, carbamazepine. Don’t know why they work. 3) Atypical antipsychotics (recent)  Strong drugs that calm you down. They’re essentially being used as tranquilizers for the manic phase as opposed to antipsychotics. Don’t have the terrible motor side-effects of the typical antipsychotics. Lessen arousal levels. DRUGS FOR DEPRESSION (Detail) TRICYCLIC ANTIDEPRESSANTS (LATE 1950’S) Examples:  Amitriptyline (tertiary)  Imipramine (tertiary),  Nortriptyline (secondary)  Desipramine (secondary) Mechanism:Block reuptake of 5HT (especially tertiary) and NE (especially nd rd secondary). However, a lot of cross-conversion occurs in the body ( e.g., 2  3 ) Time to act: 2 weeks plus Side effects:  NORMALS: drowsiness, fatigue. Do not make normal people happy  DEPRESSED PEOPLE: Improvement of mood along with side effects: o Anticholinergic  antimuscarinic-cholinergic in brain (dry mouth, etc.)  Essentially parasympathetic (smooth muscle) loss of function o Sedation because they tend to block H1 receptors) o Cardiotoxic – muscarinic system slows heart whereas NE speeds heart; confused o Orthostatic hypotension – block NE in periphery, giving you hypotension o Mania – can switch depression into mania in a bipolar person Dangers of the tricyclics:  You’re blocking the reuptake of NE. This also occurs in the body. NE receptors are part of the sympathetic nervous system and raise blood pressure, so you have to be careful.  Drug interactions: potentiate pressor drugs (drugs that increase blood pressure); don’t combine with MAOI’s. o You have to be ESPECIALLY careful when taking tricyclics with MAOIs because MAOIs are notorious for raising blood pressure Note: Probably stronger than the SSRI’s, although with more side effects  So these are reserved for individuals who don’t respond to SSRIs or SNRIs MAOI’S (monoamine oxidase A+B in
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