Lecture 10 - Antidepressants, Bipolar, & Antipsychotics Flashcards
What is reactive (secondary) depression?
Temporary reaction to real stimuli (grief, illness)
What is the treatment for reactive depression?
Psychotherapy
What is bipolar disorder?
Recurrent major depressive episodes w/ intervening manic, hypomanic, or mixed episodes
What is major depression?
One or more major depressive episodes free of manic, mixed, or hypomanic episodes
Which gender is major depression more common in?
Females
What are some emotional symptoms of major depression?
- Persistent diminished ability to experience pleasure
- Loss of interest in usual activities
- Pessimistic outlook
- Anxiety
What are some physical symptoms of major depression?
- Chronic fatigue
- Terminal insomnia (waking up very early and not being able to fall back asleep)
- Appetite disturbances
What are some cognitive symptoms of major depression?
- Poor concentration, slow thinking, poor short-term memory
- Confusion
What are some psychomotor symptoms of major depression?
- Slowed physical movements and speech
- Agitation
What is needed for a diagnosis of depression?
At least 5 symptoms every day for 2 weeks
What are some non-pharm therapies for major depression?
- Psychotherapy
- ECT
What is the amine hypothesis?
Depression is related to decreased synaptic levels of NE and serotonin
How are most antidepressants believed to work?
Enhance synaptic amines by blocking normal NT reuptake processes
What is phase 1 amine enhancement?
Short term (minutes to hours); uptake inhibition
What is phase 2 amine enhancement?
- Long term (weeks) effects of phase 1 enhancement
- Produces further enhanced amine levels to reach therapeutic significance
What does phase 1 amine enhancement cause?
Homeostatic agonist down-regulation of pre-synaptic receptors that feedback inhibit to stop amine release, to maintain “normal” agonist-to-receptor interaction levels, causing decreased negative feedback and increased phase 2 amines
Pre-synaptic receptor downregulation correlates w/ _____
Improved mood
What are examples of TCAs?
Amitriptyline and imipramine
What is the mechanism of TCAs?
- Mixed NE and serotonin reuptake inhibitors
- Also some blockade of cholinergic, histaminergic, alpha 1 adrenergic receptors causing adverse effects
What are TCAs also used for?
Neuropathic pain
What is the symptom of TCA overdose?
Cardiac arrhythmias
What are drug interactions w/ TCAs?
- CYP 2D6 inhibitors
- Sedatives, antimuscarinics, sympathomimetics
What are examples of SSRIs?
Fluoxetine, paroxetine, sertraline, and citalopram
What is the mechanism of SSRIs?
Block serotonin reuptake much more than NE
Are SSRIs more effective than TCAs?
No
What are some advantages to SSRIs over TCAs?
- Have much less cholinergic, histaminergic, and adrenergic receptor blockade so milder side effects
- Much more favourable therapeutic index
- Smaller chance of additive drug interactions
What are symptoms of paroxetine withdrawal?
- Dizziness
- Nausea
- Tremor
- Anxiety
What are drug interactions w/ SSRIs?
Strong CYP 2D6 inhibitors, TCAs, antipsychotics, beta-blockers interfere w/ metabolism
What are examples of SNRIs?
Venlafaxine, duloxetine, and desvenlafaxine
What is the mechanism of SNRIs?
- Inhibit both NE and serotonin reuptake
- Weak dopamine reuptake inhibitors
- No affinity for alpha 1 adrenergic, muscarinic, or histaminergic
What are advantages to SNRIs over SSRIs/TCAs?
- May be useful for depression w/ neuropathic pain
- Fewer drug interactions
What are examples of atypical antidepressants?
- Mirtazapine
- Bupropion
What is the mechanism of mirtazapine?
- Blocks alpha 2 receptors, thus increases NE release
- Low affinity for muscarinic, alpha 1 receptors
- Potent histamine receptor blocker
What are drug interactions w/ mirtazapine?
None known
What are advantages to mirtazapine?
- As tolerable as SSRIs
- Anxiolytic/sedative effect can be useful
- Minimal cholinergic/adrenergic drug interactions
- Weight gain major drawback
What is the mechanism of bupropion?
- Doesn’t inhibit NE or serotonin reuptake
- Weakly blocks dopamine reuptake
- Mild stimulant
- Low affinity for muscarinic, histaminergic, and alpha 1 receptors
What are some drug interactions w/ bupropion?
- Meds that lower seizure threshold (L-Dopa)
- CYP 2D6 inhibitors
What are some advantages to bupropion?
- As tolerable as SSRIs
- Stimulant effects may be helpful
- May offer relief from SSRI/SNRI-induced sexual dysfunction or weight gain
What are some examples of monoamine oxidase inhibitors?
- Phenelzine
- Tranylcypromine
- Moclobemide
What does MAO-A do?
Breaks down NE and serotonin
What does MAO-B do?
Breaks down dopamine
Tranylcypromine is a ____ inhibitor
MAO-A and B
Moclobemide is a ____ inhibitor
MAO-A
When are MAO inhibitors used?
Px unresponsive to other treatment due to side effects or food/drug interactions
What are some drug interactions w/ MAO inhibitors?
Serotonin syndrome w/ TCAs, SSRIs, or SNRIs
Pharmacologic therapy is effective in majority of major depression px after ______
Therapeutic lag period
What are the first line treatments for major depression?
SSRIs and SNRIs
What is schizophrenia?
Chronic psychosis w/ deterioration of functional capacity
Which gender does schizophrenia affect more often?
Males
What are some positive symptoms of schizophrenia?
- Delusions (most common)
- Hallucinations
- Disorganized speech
What are some negative symptoms of schizophrenia?
- Avolition - lack of motivation, desire, and persistence
- Alogia - poverty of speech
- Anhedonia - inability to feel pleasure
- Lack of emotional response
What are some cognitive symptoms of schizophrenia?
Decrease in attention, language, memory, executive function
Which symptoms of schizophrenia are likely present before any others?
Cognitive symptoms
What are affective symptoms of schizophrenia?
Blunted, inappropriate, odd expression
How do positive schizophrenia symptoms result?
Too much mesolimbic dopamine pathway activity
How do negative schizophrenia symptoms result?
Low doapminergic activity in mesocortical pathway
What occurs in the mesolimbic pathway?
Dopamine binds to nucleus accumbens, which controls motivation, reward, addiction, and reinforcing behaviour
What occurs in the mesocortical pathway?
Dopamine D1 binds to prefrontal cortex, controlling cognition, social function, and stress response
What do most antipsychotics block?
D2 dopamine receptors (mesolimbic system)
Which drugs can produce psychosis?
Drugs that increase dopaminergic activity
What is the mechanism for typical antipsychotics?
Antagonism of D2 receptors in mesolimbic system
Which symptoms are relieved w/ typical antipsychotics?
Positive
What are examples of typical antipsychotics?
- Chlorpromazine
- Fluphenazine
- Haloperidol
- Thiothixene
What causes adverse effects of typical antipsychotics?
Receptor non-selectivity and blockade of non-mesolimbic D2 dopaminergic pathways
What is the most important alpha 1 blocker side effect?
Orthostatic hypotension
What does D2 blockade in the nigrostriatal pathway cause?
Extrapyramidal side effects (Parkinson’s syndrome or pseudo-parkinsonism, restlessness, acute dystonic reactions)
What occurs in the nigrostriatal pathway?
Dopamine D2 goes from substantia nigra to striatum
What occurs in the tuberoinfundibular pathway?
Dopamine goes from hypothalamus to pituitary
What does D2 blockade in the tuberoinfundibular pathway cause?
Increased prolactin production
What effect does dopamine normally have on prolactin?
Suppresses prolactin release
What is a symptom of thioridizine overdose?
Cardiac arrhythmias
What are advantages of atypical antipsychotics?
- Block D2 in nucleus accumbens causing decrease in positive symptoms
- Decreased D2 in nigrostriatal system causes decreased EPS
- Block serotonin receptors causing decreased negative symptoms
How can you decrease negative symptoms?
By increasing mesocortical dopamine
What is the mechanism of clozapine?
Seems to have greater effect at D4 and little effect at D2 receptors
What is aripiprazole used as?
An enhancer for antidepressants
What is the mechanism of aripiprazole?
D2 partial agonist
What are the adverse effects of atypical antipsychotics?
Same as typical antipsychotics but w/ lower risk
What is a major side effect of clozapine?
Seizures
Which CYP enzymes is clozapine metabolized by?
1A2 and 3A4
What is an activator of CYP 1A2?
Smoking
How long does mania last?
Over a week
What is hypomania?
Briefer duration and less severe manic symptoms
What is bipolar 1 disorder?
Episodes of sustained mania, usually w/ intervening depressive episodes
What is bipolar 2 disorder?
Major depressive episodes w/ at least 1 manic episode
What is the mechanism of bipolar disorder?
Multiple defects, not fully understood
What are some non-pharm treatments for bipolar disorder?
Adjust sleep, nutrition, exercise, or stress levels
What are some examples of mood stabilizers?
- Lithium
- Valproate
- Lamotrigine
- Carbamazepine
What are some pharmacologic treatments for bipolar disorder?
- Mood stabilizers
- Atypical antipsychotics
- Adjunct therapy w/ BZDs
Which treatments can control manic episodes?
- Lithium, valproate, carbamazepine
- Atypical antipsychotics
- BZDs
Which treatments can control depressive episodes?
- Lithium
- Lamotrigine
- Antipsychotics
- Antidepressants
What effects does lithium have?
- Decreased serotonin reuptake
- Decrease dopamine synthesis
- Increased GABAergic activity
- Increased glutamate reuptake
- Decreased neuronal Ca reuptake
Lithium has a ___ therapeutic index
Low
What is carbamazepine used for?
Manic and depressive episodes and maintenance
What is the BZD of choice for bipolar disorder?
Clonazepam
Which antipsychotics are best for depressive episodes of bipolar disorder?
Olanzapine and fluoxetine together
Which treatments are used for maintenance therapy of bipolar disorder?
- Lithium
- Lamotrigine
- Valproate
- Carbamazepine
- Psychotherapy
