What is reactive (secondary) depression?
- temporary reaction to real stimuli such as grief or illness
- tx is mostly by psychotherapy
What is considered major depression?
- one or more major depressive episodes free of manic, mixed or hypomanic episodes
What is the lifetime prevalence of depression? When foes it usually onset?
- 6% in males and 20.4% in females
- onset is frequently 25-44 years of age
What are the emotional sx of major depression?
- inability to experience pleasure
- loss of interest in usual activities
- pessimistic outlook
- anxiety
What are the physical sx of depression?
- chronic fatigue, terminal insomnia, appetite disturbances
What are the cognitive symptoms of depression?
poor concentration, slow thinking, poor short term memory
- confusion
What are the psychomotor sx of depression?
- slowed physical movements and speech
- agitation
What are the common non-pharm therapies for depression?
psychotherapy and ECT
What is the amine hypothesis?
- depression is related to reduces synaptic levels of NE and 5HT
- autopsy showed reduced NE and 5HT metabolism in depressed suicide victims
- – this predicts that the amine NT are not being synthesized sufficiently
- most antidepressant drugs work by enhancing synaptic monoamines - do this by blocking normal neurotransmitter reuptake processes
What are the 2 phases of drug action in the synapse?
Phase 1- amine enhancement
- short term (min-hours); uptake inhibition
Phase 2- amine enhancement
- long term (weeks) effects of phase 1 enhancement - produces further enhances amine levels to reach therapeutic significance
— longer term effects cause presynaptic auto-receptor down regulation
Understanding phase 2..
- normal scenario: presynaptic receptors feedback inhibit to stop the release of amines
- phase 1 causes homeostatic down regulation of these receptors to maintain “normal” agonist: receptor interaction levels- you have fewer inhibitory auto receptors here
- results in negative feedback and phase 2 amine release
What is the cellular feature that can be seem to correlate with improved mood?
presynaptic receptor down regulation directly correlates with improved mood
- down regulation occurs on a timescale that is quite common to the time that you get improvement in mood
What are the different classes of antidepressants?
- MAO inhibitors
- TCAs
- SSRIs
- SNRIs and atypicals
Tricyclic Antidepressants
examples: amitriptyline, Imipramine, clomipramine, doxepin, protriptylline, desipramine
- Mechanism: mixed NE and 5HT reuptake inhibitors
- great variation in relative NE:5HT reuptake blockade potencies
- also used in neuropathic pain(NET effect)
- ALSO blocks cholinergic, histaminergic, a1 adrenergic receptors
What are the adverse effects of TCAs?
- antimuscarinic, cardiovascular (orthostatic hypotension, conduction defects), sedation, sympathomimetic (tremor, insomnia), neurologic (seizures), metabolic (weight gain, sexual disturbances), overdose (dangerous cardiac arrhythmias)
What are the drug interactions associated with TCAs?
- pharmacokinetic: CYP 2D6 inhibitors, highly protein bound
- pharmacodynamic: sedatives, sympathomimetics, antimuscarinics
What are the drug interactions associated with SSRIs?
- ex: fluoxetine, paroxetine, sertraline, citalopram
- MOA: block serotonin reuptake more effectively than NE
- no more effective than TCAs
- fluoxetine was used first - paroxetine and sertraline have shorter half lives- citalopram is the most SERT selective
- also drug interaction differences
What are the adverse effects of SSRIs?
- much less cholinergic, histaminergic, adrenergic receptor blockade than TCAs- more tolerable side effect profile
- safer than o/d
- associate with mild, short lived GI symptoms, headache
- sexual dysfunction, fatigue, insomnia can be problems
- paroxetine withdrawal - dizziness, nausea, tremor, anxiety
- platelet inhibition
What are the drug interactions associated with SSRIs?
Pharmacokinetic: strong CYP 2D6 inhibitors, TCAs, antipsychotics, beta blockers interfere with metabolism.
Pharmacodynamic: low non SERT interactions
What is the advantage of using SSRIs over TCAs?
- have equal efficacy with milder side effect profile
- much more favourable TI
- smaller chance of having additive drug interactions
SNRIs?
- examples: venlafaxine, duloxetine, desvenlafaxine
- MOA: inhibits both serotonin and NE reuptake, but NOT TCA
- also weak dopamine reuptake inhibitors
- no affinity for muscarinic, a1 adrenergic or histaminergic receptors
What are the adverse effects of SNRIs?
- much lower incidence than TCAs, similar to SSRIs
- can include nausea, sweating, dizziness, anxiety, sexual dysfunction, hypertension
What are the drug interactions?
- limited pharmacodynamic
- protein binding varies: venlafaxine 30%, duloxetine >90%
- CYP 2D6 substrate
What is the advantage of SNRIs over SSRIs/TCAs?
- have a milder side effect profile over SSRIs?
- may be useful for depression with neuropathic pain
- fewer drug interactions
- potentially lower safety margin than SSRIs in O/D
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Anatomy and Physiology of Pain62
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Opiods62
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Epilepsy46
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Antipsychotics24
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Bipolar disorder20
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Antidepressants32
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Anxiolytics and Hypnotics61
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Drugs of Abuse65
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Addiction Pharmacotherapy34
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Antiviral Drugs70
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Antifungals37
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Antibiotics 122
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Antibiotics 2105
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Antibiotics 315
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Antibiotics 435
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Diuretics57
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Lipid Disorders43
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Antihypertensives61
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Antianginals38
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Drugs for Heart Failure38
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Drugs for Heart Failure 236
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Antiarrhythmatics46
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Antiarrhythmatics part 258
