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5 types of antidepressant groups
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- Serotonin-Norepinephrine Reuptake Inhibitors
DSM Symptoms of Depression
- 5 or more of the following for several weeks:
- Depressed mood most of the day, every day
- Diminished interest/pleasure in most activities most of the day, every day
- Changes in body weight/appetite
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue/loss of energy
- Feelings of worthlessness or excessive guilt
- Diminished ability to think/concentrate; indecisiveness
- Recurrent thoughts of death/suicide with or without a specific plan
6 Different Types of Depression
- Major, non-psychotic depression
- Minor depression
- Bipolar depression
- Psychotic depression
- Secondary depressions
Less severe but more chronic and longer lasting than major, non-psychotic depression
3 key regions in emotional processing in brain:
- Medial PFC
- Subgenual ACC
3 key regions in motivational processing in brain:
- Ventral tegmental area (VTA)
- Nucleus accumbens
3 key regions in higher cognitive processing in brain:
- Parietal cortex
- medial PFC
- Negative feedback loop involved in stress response
- Hypothalamus releases corticotropin releasing factor (CRF), causing the pituitary to release adrenocorticotropic hormone (ACTH), causing the adrenal gland to release glucocorticoids, which negative feedbacks the hypothalamus
- Stress increases glucocorticoid levels
Three Treatment Approaches to Depression:
- Somatic: physical (medication, ECT, TMS, etc...)
- Psychotherapeutic: evidence-based therapies (e.g. CBT)
- Therapeutic lifestyle changes: e.g. exercise, nutrition, etc...
Pharmacotherapeutic approach to non-psychotic unipolar depression
Pharmacotherapeutic approach to psychotic unipolar depression
Antidepressant and antipsychotic
Pharmacotherapeutic approach to bipolar depression
Mood stabilizer and possibly antidepressant
Pharmacotherapeutic approach to depression linked to substance abuse
Detoxification as a first step
Locus coeruleus releases which neurotransmitter?
Norepinephrine is relesed by what brain region?
Locus coeruleus in the pons
The Raphae nuclei release which neurotransmitter?
Serotonin is released by which brain region?
Raphae nuclei in the pons
Short term and long term influences of antidepressants:
- Short term: some block reuptake of NE and/or 5-HT
- Long term: influence long term changes enhancing cellular protection
Why do antidepressants take so long to work?
- NOT due to pharmacokinetics (half-life ~1 day)
- Due to the long term changes in enhancing cellular protection
- Typically take 4-6 weeks to act
Specifically, describe the long-term effects of antidepressants.
- By blocking reuptake, there is more NE and/or 5-HT in synapse
- This leads to having weeks of increased second messenger systems
- Leads to more transcription of proteins that allow for growth of synapses and healthier neuronal cells
Relation between stress and BDNF
More stress --> more glucocorticoids --> less BDNF --> cell atrophy and decreased survival
Relation between antidepressants and BDNF
Antidepressants --> more NE and/or 5-HT --> more BDNF --> increased cell growth and survival
Two secondary amine TCAs:
Amitriptyline (secondary or teritary amine?)
Imipramine (secondary or tertiary amine?)
Nortriptyline (secondary or tertiary amine?)
Desipramine (secondary or tertiary amine?)
Binding of tricyclic antidepressants to these 3 receptor types contributes to side effects:
- Histamine receptors (H1 and H2)
- alpha-adrenergic receptors
What do tricyclic antidepressants do that contribute to their antidepressant effects?
Block NE and 5-HT reuptake
Antimuscarinic (anticholinergic) side effects of TCAs:
- blurred vision
- dry mouth
- urinary retention
- memory dysfunction
- speech blockage
- decreased sweating
Antihistamine (H1) side effects of TCAs:
Antihistamine (H2) side effects of TCAs:
mental confusion (?)
Anti-alpha-adrenergic side effects of TCAs:
- orthostatic hypotension
Sudden drop in blood pressure and resulting light-headed feeling when you stand up
VOD of TCAs is large or small?
Half-life of TCAs
Which TCA is converted into an active metabolite (another TCA), and what is the name of the active metabolite?
Amitriptyline ----> Nortriptyline
What does "PRN" mean?
Medication taken as needed
3 examples of SSRIs:
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
- Citalopram (Celexa)
Half-life of fluoxetine
Half-life of sertraline
Typical side effects of SSRIs:
- Sexual dysfunction
- Asthenia (tiredness)
2 examples of SNRIs:
- Venlafaxine (Effexor)
- Duloxetine (Cymbalta)
These drugs are similar to TCAs, but are better in that they don't have as many side effects
3 examples of MAO-Is:
- Phenelzine (Nardil)
- Cypromine (Parnate)
- Isocarboxazid (Marplan)
Effects associated with an overdose of SSRIs or with drug interactions of MAO-Is
Symptoms of serotonin syndrome:
- Severe agitation
- Disorientation and confusion
- Muscle spasms
- Fever, shivering, chills
- Elevated blood pressure
- Increased heart rate
An enzyme that breaks down dopamine, norepinephrine, and serotonin
What substance typically broken down by MAO A in the gut cannot be eaten when on MAOIs?
Drug interactions of MAO-Is can lead to these two severe side effects:
- Hypertensive crisis
- Serotonin syndrome
Interactions of MAO-Is with what drugs can lead to hypertensive crisis?
Interactions of MAO-Is with what drugs can lead to serotonin syndrome?
Bupropion affects which neurotransmitter?
What's important about the antidepressant effects of ketamine?
- Low doses given IV can have a rapid antidepressant effect that lasts for days
- However, has many behavioral side effects (similar to those of PCP), but these are minor at low doses
Ketamine blocks which receptor?