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5 types of antidepressant groups
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- SSRIs
- Serotonin-Norepinephrine Reuptake Inhibitors
- Bupropion
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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
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6 Different Types of Depression
- Major, non-psychotic depression
- Dysthymia
- Minor depression
- Bipolar depression
- Psychotic depression
- Secondary depressions
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Dysthymia
Less severe but more chronic and longer lasting than major, non-psychotic depression
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3 key regions in emotional processing in brain:
- Medial PFC
- Subgenual ACC
- Amygdala
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3 key regions in motivational processing in brain:
- Ventral tegmental area (VTA)
- Nucleus accumbens
- PFC
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3 key regions in higher cognitive processing in brain:
- dlPFC
- Parietal cortex
- medial PFC
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Hypothalamic-pituitary axis:
- 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
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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...
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Pharmacotherapeutic approach to non-psychotic unipolar depression
Antidepressant
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Pharmacotherapeutic approach to psychotic unipolar depression
Antidepressant and antipsychotic
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Pharmacotherapeutic approach to bipolar depression
Mood stabilizer and possibly antidepressant
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Pharmacotherapeutic approach to depression linked to substance abuse
Detoxification as a first step
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Locus coeruleus releases which neurotransmitter?
Norepinephrine
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Norepinephrine is relesed by what brain region?
Locus coeruleus in the pons
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The Raphae nuclei release which neurotransmitter?
Serotonin
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Serotonin is released by which brain region?
Raphae nuclei in the pons
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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
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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
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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
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Relation between stress and BDNF
More stress --> more glucocorticoids --> less BDNF --> cell atrophy and decreased survival
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Relation between antidepressants and BDNF
Antidepressants --> more NE and/or 5-HT --> more BDNF --> increased cell growth and survival
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Two secondary amine TCAs:
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Amitriptyline (secondary or teritary amine?)
Tertiary
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Imipramine (secondary or tertiary amine?)
Tertiary
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Nortriptyline (secondary or tertiary amine?)
Secondary
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Desipramine (secondary or tertiary amine?)
Secondary
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Binding of tricyclic antidepressants to these 3 receptor types contributes to side effects:
- mAChR
- Histamine receptors (H1 and H2)
- alpha-adrenergic receptors
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What do tricyclic antidepressants do that contribute to their antidepressant effects?
Block NE and 5-HT reuptake
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Antimuscarinic (anticholinergic) side effects of TCAs:
- blurred vision
- glaucoma
- dry mouth
- constipation
- urinary retention
- memory dysfunction
- speech blockage
- decreased sweating
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Antihistamine (H1) side effects of TCAs:
sedation, drowsiness
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Antihistamine (H2) side effects of TCAs:
mental confusion (?)
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Anti-alpha-adrenergic side effects of TCAs:
- orthostatic hypotension
- tachycardia
- arrythmias
- dizziness
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Sudden drop in blood pressure and resulting light-headed feeling when you stand up
Orthostatic hypotension
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VOD of TCAs is large or small?
Large
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Half-life of TCAs
18-25 hrs
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Which TCA is converted into an active metabolite (another TCA), and what is the name of the active metabolite?
Amitriptyline ----> Nortriptyline
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What does "PRN" mean?
Medication taken as needed
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3 examples of SSRIs:
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
- Citalopram (Celexa)
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Half-life of fluoxetine
87 hours
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Half-life of sertraline
26 hours
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Typical side effects of SSRIs:
- Sexual dysfunction
- Nausea
- Vomiting
- Diarrhea
- Anorexia
- Anxiety
- Asthenia (tiredness)
- Insomnia
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2 examples of SNRIs:
- Venlafaxine (Effexor)
- Duloxetine (Cymbalta)
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These drugs are similar to TCAs, but are better in that they don't have as many side effects
SNRIs
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3 examples of MAO-Is:
- Phenelzine (Nardil)
- Cypromine (Parnate)
- Isocarboxazid (Marplan)
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Effects associated with an overdose of SSRIs or with drug interactions of MAO-Is
Serotonin syndrome
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Symptoms of serotonin syndrome:
- Severe agitation
- Disorientation and confusion
- Ataxia
- Muscle spasms
- Fever, shivering, chills
- Diarrhea
- Elevated blood pressure
- Increased heart rate
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An enzyme that breaks down dopamine, norepinephrine, and serotonin
Monoamine oxidases
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What substance typically broken down by MAO A in the gut cannot be eaten when on MAOIs?
Tyramine
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Drug interactions of MAO-Is can lead to these two severe side effects:
- Hypertensive crisis
- Serotonin syndrome
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Interactions of MAO-Is with what drugs can lead to hypertensive crisis?
- Sympathomimetics
- L-DOPA
- TCAs
- Venlaxafine
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Interactions of MAO-Is with what drugs can lead to serotonin syndrome?
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Bupropion affects which neurotransmitter?
Dopamine
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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
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Ketamine blocks which receptor?
NMDA
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