Antidepressants Flashcards
What is the hypothesis behind mood
major depressive disorders result from a functional deficiency of NE or 5-HT at synapses in CNS
Neurotropic and endocrine components
Neurotropic hypothesis of major depression is
Changes in tropic factors and hormones play a major role
Successful treatment results in changes in:
CREB (cAMP response element binding)
BDNF (brain derived neurotrophic factor
What do monoamine NT do and how do antidepressants take advantage
Carry messages between cells
Initiate cascade of events
Reabsorbed back into nerve cells
-Most antidepressants inhibit transporter reuptake molecules so the NT stay in the synapse longer
What is the amine hypothesis of major depression and how do antidepressants use this
Depression is associated with changes in serotonin or NE
Many antidepressants cause changes in amine signaling!
What neuroendocrine factors are associated with depression
Thyroid dysregulation
Estrogen deficiency
Testosterone deficiency
More severe depression: Abnormal HPA axis, elevated cortisol
What are the phases of MDD treatment
Acute: 6-12 weeks. goal is remission (eliminate Sx)
Continuation: 4-9 months after remission. goal is prevent relapse and eliminate residual Sx
Maintenance: 12-36 months. goal is prevent recurrence
What meds are associated with inducing depressive Sx
Isotretinoin Anticonvulsants Triptans BB, clonidine, methyldopa, reserpine Hormone therapy interferons varenicline (smoking cessation)
What drugs are used as antidepressants
TCA MAOI SSRI SNRI 5HT2 heterocyclic antidepressants
What is the PK of antidepressants (general overview)
Rapid oral absorption Peak plasma in 2-3 hours Tightly bound to plasma proteins Hepatic metabolism Renally cleared
Antidepressants can be used to Tx
MDD panic disorder GAD PTSD OCD Neuropathic pain, fibromyalgia, PMDD, menopause vasomotor Sx, stress incontinence
What are TCA
Block re-uptake transporters of NE and 5-HT
Used in MDD, *chronic pain, *enuresis, and insomnia
-Amitriptyline, Imipramine, Desipramine, Doxepin, Nortriptyline
What are ADE of TCA
muscarinic block (anticholinergic)
sedation
weight gain
OD: arrhythmia, seizure
What are the most potent TCA’s
Most potent 5-HT blockers: Ami, Imi
Most potent NE blocker: Desi, Nor
-highest potency drugs have the most ADE!
What are MAO inhibitors
Inhibit monoamine oxidases that normally metabolize NE and serotonin (type A) and dopamine (type B)
Used in unresponsive MDD, anxiety, panic d/o
Selegiline in parkinson’s (MAO-B)
-Phenelzine, Tranylcypromine, selegeline
MAOI interact with what drugs
Tyramine and sympathomimetics: cause HTN
SSRI: cause serotonin syndrome
Toxicities of MAOI are
Hypotension
Insomnia
Those on MAOI should avoid these foods (only a few big ones)
dairy beer wine canned aged meat sardines liver yeast pod beans chocolate coffee licorice soy sauce
What are SSRIs
Selectively inhibit 5-HT transporters w/ modest effects on other NT (fluoxetine and paroxetine mildly block NE)
Used for MDD, GAD, PTSD, OCD, panic d/o, PMDD, bulimia
-Citalopram, Escitalopram, Fluoxetine*, Paroxetnie, Sertraline
SSRI interact with
Warfarin*: alprazolam and theophylline increase blood levels
lithium
TCA
ADE of SSRI are
anxiety, insomnia, nausea, serotonin syndrome, sexual dysfunction
citalopram: QT prolongation
fluoxetine: anorexia
fluvoxetine: somnolence
paroxetine: anticholinergic ADE (mildly blocks NE)
Bolded dosing info on SSRI’s
Citalopram: do not dose >40mg/d to avoid QT prolongation risk
Escitalopram: can increase to max dose after 1 week
What ADE is common to all antidepressants
Suicidality; Increased risk if <24, Decreased risk if >65
Monitor for behavioral changes and mental status
What are SNRI
heterocyclic drugs that block NE and 5HT transporters but LACK alpha blocking, anticholinergic, and antihistaminic actions of TCA
Used for MDD, FAD, neuropathies, fibromyalgia, SUI, and menopause vasomotor Sx
-Venlafaxine*, duloxetine, levomilnacipran
ADE of SNRI are
HTN/tachy , insomnia, nausea, serotonin syndrome, sexual dysfunction dose dependent HTN: venlafaxine orthostatic hypotension: Duloxetine HLD: desvenlafaxine Seizures (venlafaxine, desvenlafaxine)
Bolded dosing info on SNRI newer generation
Desvenlafaxine ADE are increased with higher dose, but benefits do not increase with dose
Venlafaxine: reduce dose if sustained HTN occurs
What are mixed 5-HT2 antagonists/5-HT1a enhancers
Block 5-HT2 receptors with minor effects on amine transporters
Used for MDD and hypnotics
-Trazodone, Nefazodone, Vilazodone, Vortioxetine
ADE of mixed serotonergics are
Nef: hepatic toxicity Traz: sedation, orthostatic hypotension Vila: serotonin syndrome, decreased male libido Vori: GI and sexual dysfunction Depression and anxiety Depression with cognitive difficulties
What is Buproprion
NE and dopamine reuptake inhibitor
Used in smoking cessation and MDD
May cause seizures (dose related, and increased w/ alcohol withdrawal, head trauma, CNS tumor)
What is Miratazepine
Presynaptic a2 blocker w/ some effect on 5-HT
Used for sedation
May cause sedation and weight gain
Choose an antidepressant based on
indication cost availability ADE potential drug interactions Pt Hx Pt preference age and gender medical status
What are non-med options in treating depression
Electorconvulsive therapy
Repetitive Transcranial Magnetic Stimulation
What supplements an help Tx depression
Omega 3 fatty acids (EPA +/- DHA): used to augment Tx of MDD
St john’s wort: mild-mod MDD. induces hepatic metabolic enzymes
SAMe: under review by task force
Folate: involved in synthesis of new NT, like 5-HT. Reasonable to augment MDD Tx with the 3 compounds
What are the 3 folate compounds used in augmenting Tx of MDD
Folic acid
Folinic acid
5-Methyltetrahydrofolate
Does exercise play a role in treating depression
Yes! a recent study even confirmed the benefit of exercise on depression
16 kcal/kg/wk exercise associated with greater remission rates in conjunction with an SSRI
Task force says to include exercise in Tx of MDD!
