Studied by 27 peopleDescribe the clinical presentation of depression
SIGE CAPS (Sleep disorders, interest loss, guilt, energy deficient, concentration, appetite, psycho motor fluctuations, suicidal ideation)
Describe the diagnostic criteria for depression
five or more of the SIGECAPS symptoms have been present during the same two week. Including depressed mood or anhedonia (no pleasure) AND symptoms do not coincide with mania AND These symptoms are clinically distressing and cause impairment in multiple settings AND the symptoms are not directly related to a physiological or drug induced cause
what are some drugs that can induce depression
antihypertensives (beta blockers (esp propranolol) Clonidine, methyldopa, reserpine), CNS depressants (alcohol, barbiturates, antielliptics), hormonal agents (corticosteroids, contraceptives, tamoxifen), isotretinoin, interferon, efavirenz
Describe dysthymic disorder
depressed mood on most days for more than two years, low grade chronicity (more than 2 SIGE CAPS symptoms), never been without symptoms for more than two months for 2 years, Does not meet criteria for major depressive disorder
describe major depression with psychotic features
most severe form of depression, hallucinations are usually auditory hallucinations such as voices, and includes delusions (fixed false beliefs)
describe melancholic depression
lack of pleasure in all or almost all activities OR lack of reactivity to usually pleasurable stimuli. (distinct from depressed mood seen with grief, depression worsened the mornings, increased early morning awakenings, marked psycho motor retardation, significant anorexia, excessive guilt)
describe atypical depression
mood brightens with positive events, significant weight gain, hypersomnia, leaden paralysis, interpersonal rejection sensitivity
What is involved in a mental status exam
General appearance, behavior, and speech. Mood and affect, level of intellectual functioning, thought processes.
What are risk factors for suicide
insomnia, anxiety, life stressor, adjustment disorder
What are some questionnaires to evaluate depression
PHQ 9, Montgomery asberg, Hamilton
What is considered a response to antidepressant therapy
an improvement of symptoms, a 50% or more decrease in HAM-D or MADRS
what is considered remission in antidepressant treatment
returning to Wellness or disappearance of symptoms, most frequently measured as HAM-D greater than or equal to 7 or MADRS greater than or equal to 10
what is considered recovery in antidepressant treatment
remission for two months or more
What is considered relapse in antidepressant treatment
return of symptoms after remission
What is considered recurrence in antidepressant treatment
return of symptoms after recovery
what are the monoamine neurotransmitters
Serotonin, norepinephrine, epinephrine, dopamine, and histamine
what are the catecholamine neurotransmitters
dopamine, norepinephrine, and epinephrine
what are the indoleamine neurotransmitters
serotonin
What is a precursor for dopamine
L tyrosine
what enzyme controls the rate limiting step in dopamine production
tyrosine hydroxylase
What receptor is on the surface of vesicles that hold dopamine
VMAT2
how many families of receptors are there for dopamine
2
what are the families of receptors for dopamine
D1 and D2
What transporters control the reuptake of dopamine
dopamine and norepinephrine transporter
what reuptake transporter is not present in the prefrontal cortex
the dopamine reuptake transporter
where can you not find the dopamine reuptake transporter
in the prefrontal cortex
what enzymes are responsible for the metabolism of dopamine
MAOA and MAOB
Which dopamine receptor family is found on the presynaptic nerve
D1
Which dopamine receptor family is found on the postsynaptic nerve
D2
What is the second messenger system that is associated with the D1 receptor family
increase cAMP via Gs, increase PIP2 hydrolysis, calcium mobilization, PKC activation
What is the second messenger system that is associated with the D2 receptor family
Decrease cAMP, increase potassium currents, decrease voltage gated calcium channels
what receptors are in the D1 receptor family and where can you find them
D1-Stratum, neocortex. D2-hippocampus, hypothalamus
what receptors are in the D2 receptor family and where can you find them
D2-stratum, substantia nigra, pituitary gland. D3-Olfactory tubercle, nucleus, accumbens, hypothalamus. D4-frontal cortex, medulla, midbrain
Where in the body does dopamine exert its effects
heart and vasculature, kidney, CNS
What effect does dopamine have on the heart and vasculature
D1 receptor binding leads to vasodilation and decreased cardiac afterload. At high concentrations, circulating dopamine activates alpha adrenergic receptors leading to vasoconstriction
what effect does dopamine have on the kidneys
maintains renal blood flow and glomerular filtration. Influences renin angiotensin system.
what effect does dopamine have on the CNS
Mesolimbic Tract=Reward, Learned Behavior, Mesocortical Tract=Higher order cognitive processes, Nigrostriatal Tract=Movement and locomotion, Tuberoinfundibular Tract=Prolactin secretion, Area postrema=Contains small set of intrinsic dopamine neurons (emesis)
What is a precursor for norepinephrine
dopamine
Where in the brain are norepinephrine receptors highly concentrated
prefrontal cortex and limbic areas
What roles is norepinephrine involved in
arousal, vigilance, learning, and cognition (survival)
How does a norepinephrine deficiency present itself
reduction in concentration, working memory, may cause psycho motor retardation, resulting in apathy and symptoms of depression
What is a precursor for serotonin
tryptophan
what is serotonin a precursor for
melatonin
Describe serotonin receptors and their mechanism
almost all serotonin receptors are G coupled. 5HT3 (in the gut) is ionic
Which serotonin receptor families are inhibitory
5HT-1 and 5
Which serotonin receptors act through G alpha Q
5HT-2
Which serotonin receptors are ionic
5HT-3
Which serotonin receptors are excitatory
5HT-6 and 7
how many families and subtypes of serotonin receptors are there
seven families and at least 14 subtypes of receptors
How does norepinephrine and dopamine dysfunction present
depressed mood, loss of happiness/joy, loss of interest/pleasure, loss of energy/enthusiasm, decreased alertness, decrease self-confidence
how does norepinephrine and serotonin dysfunction present
depressed mood, guild/disgust, Fear/anxiety, hostility, irritability, loneliness
What is BDNF and what role does it play in the brain
brain derived neurotrophic factor. it is involved in neuroplasticity, neurogenesis, cell survival and synaptogenesis
describe the modern theory on why it takes so long for antidepressant therapies to work
downstream mechanisms influencing treatment response, intracellular actions responsible for effects (decreased BDNF)
Describe the effect of a blockade of monoamine transporters
increased levels of circulating monoamines in the synapse, leans to downstream effects and increase in neurotrophic factors.
Describe the effects of inhibition of monoamine oxidase
leads to similar cascade as blockade of monoamine transporters (increased levels of circulating monoamines in the synapse, leans to downstream effects and increase in neurotrophic factors)
What are the five mechanisms that are used to treat depression
blockade of monoamine transporters, inhibition of monoamine oxidase, agonistic activity at 5-HT-1 receptors, blockade of 5-HT-2A receptors, antagonism of A2 autoreceptors
What is the effect of antagonism of A2 autoreceptors
increases neurotransmission of monoamines
what are some non-pharm approaches to treating depression
psychotherapeutic interventions (CBT, interpersonal therapy, marital therapy, family therapy), vagus nerve stimulation (specialty), transcranial magnetic stimulation (rare, five days per week), electroconvulsive therapy for refractory depression
What is the black box warning for antidepressive drug therapies
increased risk of suicidality in people younger than 25
what drug class is amitriptyline (Elavil®)
tricyclic antidepressant
what drug class is Imipramine (Tofranil®)
tricyclic antidepressant
what drug class is Trimipramine (Surmontil®)
tricyclic antidepressant
what drug class is Desipramine (Norpramin®)
tricyclic antidepressant
what drug class is Doxepin (Sinequan®)
tricyclic antidepressant
what drug class is Nortriptyline (Pamelor®)
tricyclic antidepressant
what drug class is Protriptyline (Vivactil®)
tricyclic antidepressant
what drug class is Maprotiline (Ludiomil®)
tricyclic antidepressant
what drug class is Amoxapine (Ascendin®)
tricyclic antidepressant
what drug class is Esketamine (Spravato®)
NMDA Antagonists
what drug class is Isocarboxazid (Marplan®)
Monoamine Oxidase Inhibitors (MAOIs)
what drug class is Phenelzine (Nardil®)
Monoamine Oxidase Inhibitors (MAOIs)
what drug class is Tranlycypromine (Parnate®)
Monoamine Oxidase Inhibitors (MAOIs)
what drug class is Selegiline (EMSAM®)
Monoamine Oxidase Inhibitors (MAOIs)
what drug class is Duloxetine (Cymbalta )
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
what drug class is Venlafaxine (Effexor)
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
what drug class is Desvenlafaxine (Pristiq®)
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
what drug class is Levomilnacipran (Fetzima®)
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
what drug class is Brexanolone (Zurlesso®), and what is it used for?
GABA Allosteric Modulation, post-partum depression
what drug is used for postpartum depression
GABA Allosteric Modulation
what drug class is Trazodone (Desyrel®)
5-HT2 Antagonists
what drug class is Nefazodone (Serzone®)
5-HT2 Antagonists
what drug class is Quetiapine (Seroquel®)
2nd Generation Antipsychotics
what drug class is Brexpiprazole (Rexulti®)
2nd Generation Antipsychotics
what drug class is Olanzapine/Fluoxetine (Symbyax®)
2nd Generation Antipsychotics
what drug class is Aripiprazole (Abilify®)
2nd Generation Antipsychotics
what drug class is Citalopram (Celexa®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Escitalopram (Lexapro®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Fluoxetine (Prozac®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Paroxetine (Paxil®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Sertraline (Zoloft®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Fluvoxamine (Luvox®)
Selective Serotonin Reuptake Inhibitors (SSRIs)
what drug class is Vilazodone (Viibryd®)
SSRI/5-HT1A partial agonist
what drug class is Vortioxetine (Trintellix®)
SSRI/5-HT1A partial agonist
what drug class is bupropion (Wellbutrin®)
Aminoketone
Describe the mechanism of action of SSRI's
1.) Block the reuptake pump, 2.)Increase somatodendritic serotonin, 3.) Desensitized autoreceptors, 4.) Neuronal impulse turned on, 5.) Increased release of serotonin from axon terminals, 6.) Desensitization of postsynaptic neurons, 7.) Downstream increases in neurotropic factors, 8.) Neurogenesis
What are the most common adverse drug effects with SSRIs
nausea and vomiting, sexual dysfunction, insomnia, headache, activation/anxiety, weight gain (less than TCA's), Potential to lower the seizure threshold
Why can SSRI's cause nausea and vomiting
effects on serotonergic receptors in the gut
How do you decrease nausea and vomiting with SSRIs
take with food
Which of the SSRI's is the most activating and therefore can cause the most insomnia
fluoxetine
Which antidepressant is the most known for lowering the seizure threshold
bupropion
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