Depression Flashcards
What is the most common diagnosis associated with psychiatric admission?
Depression
One-half of the people that commit suicide have major depression
Are most patients with depression treated?
Less than half of depressions are treated
Not seeking care, not getting the right tx
What is the presentation of depressive symptoms?
- Some patients look sad, guilt-ridden, and hopeless
- Other patients look nervous, and irritable
- Others complain of somatic problems
- Psychosis can accompany depression
- Depression can lead to a dementia-like state
What is more than 2 years of depressed mood of loss of interest but not severe enough to meet MDD?
Dysthymia
What is the criteria for major depression?
Five (or more) of the following sx present for a 2-week period: Depressed mood* Decrease interest* or pleasure Change in weight/appetite Insomnia or hypersomnia Loss of energy Feeling of worthlessness or inappropriate guilt Decreased concentration Recurrent thoughts of death Psychomotor agitation or retardation
*1 of 5 MUST be depressed mood and/or decreased interest
What is Mnemonic depression?
SIG E CAPS
S leep disturbance I nterest loss G uilt E nergy loss C oncentration difficulties A ppetite disturbance P sychomotor retardation/ agitation S uicidality
What are the CV angents/AntiHTN medications that induce depression?
Digitalis products Clonidine Methyldopa Reserpine Hydralazine Propranolol Prazosin Procainamide
What are the Misc. Agent medications that induce depression?
Disulfiram
Antineoplastic agents
What are the CNS medications that induce depression?
Amantadine L-dopa Barbiturates Chloral Hydrate Haloperidol/Phenothiazines Alcohol Amphetamine withdrawal Alpha interferon
What are the hormones medications that induce depression?
Corticosteroids
Progesterone
What are the major CNS causes of depression?
Stroke
Alzheimers Disease
MS
Huntington’s Disease
What are the major Endocrine causes of depression?
HYPOTHYROIDISM
Cushing’s/Addison’s diseases
Diabetes
What are the major autoimmune causes of depression?
RA
Systemic Lupus erthematosis
What are the major cardiovascular causes of depression?
Post-MI
CHF
What are the major other causes of depression?
Malignancies ID Malnutrition Narcolepsy Sleep apnea Pancreatic disease Metabolic disturbances Chronic Pain
What is the pathophysiology of depression?
Unknown at present
Genetic predisposition: 40-50% familial linked
Dysregulation of hippocampus and hypothalamic-pituitary-adrenal (HPA) axis
Monoamine hypothesis (DA, NE, 5-HT)
These are how all the meds used to treat depression work so this is incredibly supportive.
Impairment of neurotropic factors (eg., BDNF)
Impairment of brain reward pathways (role of subcortical pathways)
Goes along with monoamine hypothesis.
In the monoamine hypothesis what does depression result from dysregulation of what?
Norepinephrine (NE)
Serotonin (5-HT)
Dopamine (DA)
What happens post-synaptic 5-HT, DA, and NE receptors when the amount of these neurotransmitters is decreased?
Up-regulation of post-synaptic receptors
Decreased receptor sensitivity
Altered genetic expression
What happens when reserpine is administered for the monoamine hypothesis?
Reserpine
Induces depression depletion of monoamines
Depression is reversed by the 5-HT precursor and (less well) by the NE precursor
What is the monoamine hypothesis?
Low 5-HT and/or NE in limbic system leads to depression
Increased limbic 5-HT and/or NE can reverse depression
What is involved in the dysregulation of HPA axis?
Hyperactive HPA Axis Increased CRF Blunted cortisol supression May lead to hippocampal toxicity Increased glucocorticoids may result from severe stress
How does dysregulation of HPA axis work?
Hippocampus has negative feedback on the HPA loop
Glucocorticoids trigger this negative feedback
Sustained elevation of glucocorticoids seen in prolonged and severe stress
Damage the hippocampal neurons
Reduces the negative feedback “Snowball” effect
Abnormal excessive activation of HPA axis seen in 50% of depressed patients
Corrected with antidepressant treatment
What is a potent regulator of plasticity of adult neurons and glia which is important for survival of neurons?
Brain Derived Neurotropic Factor (BDNF)
What is BDNFs role?
Acute and chronic stress decreases expression of BDNF
Deficits are seen in hippocampal region of brain in depressed patients
These deficits are alleviated by antidepressant treatment
What is the effect of depression on the hippocampus?
Possibly responsible for cognitive symptoms of depression
What is the effect of depression on the nucleus accumbens & Amygdala?
Dopaminergic pathway
Deficits may lead to amotivation and anhedonia
What is the effect of depression on the hypothalamus?
Mediates numerous functions ie., sleep, appetite, circadian rhythms, interest in sex
What is the goal of Major depressive disorder (MDD)?
Reduce the acute symptoms of the depressive episode
Facilitate the patient’s return to premorbid function (prior to illness)
Recovery should be the rule, not the exception!
Prevent further episodes of depression
What are the treatment options for MDD?
Selective Serotonin Reuptake Inhibitors (SSRIs)
Tricyclic Antidepressants (TCAs)- anticholinergic SE and are less tolerated.
Bupropion
Venlafaxine
Nefazodone
Mirtazepine
Duloxetine
Monoamine Oxidase Inhibitors (MAOIs)- mainly for PD
Newer agents
What are the selective serotonin reuptake inhibitors (SSRIs)?
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine Fluvoxamine Citalpram (Celexa) Escitalopram (Lexapro)
What is the most commonly prescribed antidepressant?
SSRIs
SSRI (fluoxetine, sertraline, paroxetine, fluvoxamine, citalpram, escitalopram)- MOA
MOA: Block the reuptake of serotonin
Which is the SSRIs has the longest half life?
Fluoxetine
You can stop this abruptly unlike other SSRIs
SSRI (fluoxetine, sertraline, paroxetine, fluvoxamine, citalpram, escitalopram)- Side effects
Nausea Headache Sleep disturbances- usually resolved if taking in the morning. Changes in weight Agitation/increased anxiety (initial)- occurs initially Sexual Dysfunction Tremor Sweating Rare hyponatremia- rarely see this
Which SSRI is more likely to cause sedation, constipation and dry mouth?
Paroxetine
Does paroxetine CR have less GI side effects that paroxetine IR?
Yes
Which SSRI is more likely to have GI distress, insomnia, or activation?
Sertraline
What is the order for risk of discontinuation syndrome from highest to lowest?
Paroxetine > sertraline = citalopram = escitalopram > fluoxetine
What is involved with antidepressant discontinuation syndrome?
- Flu-like symptoms, malaise
- Dizziness
- GI (nausea, diarrhea)
- Transient changes in mood, affect, appetite, and sleep
- Electric “shock-like” sensation in upper extremities
- Vivid dreams/nightmares
- Poor concentration
What are the TCA’s used in depression?
Nortiptyline Despramine Protriptyline Amoxapine Amitriptyline Imipramine Clomipramine Doxepin
What are the secondary amine TCAS?
Nortiptyline
Despramine
Protriptyline
Amoxapine
What are the tertiary amine TCAs?
Amitriptyline
Imipramine
Clomipramine
Doxepin
TCA (Nortiptyline, Despramine, Protriptyline, Amoxapine, Amitriptyline, Imipramine, Clomipramine, Doxepin)- MOA
Block the reuptake of NE and 5-HT (NE > 5-HT)
What TCAs do you need to monitor drug levels?
Nortipyline
Despramine
Draw blood sample 12 hours past the last dose
TCA (Nortiptyline, Despramine, Protriptyline, Amoxapine, Amitriptyline, Imipramine, Clomipramine, Doxepin)- Side effects
Tachycardia
Orthostasis
Weight gain
Sedation
Sexual dysfunction
Anticholinergic effects–Dry mouth, Constipation, Dry eyes, Urinary retention
Cardiac conduction changes– Prolongation of QRS, ST depression, flattened or inverted T waves (Baseline ECG)
What side effects are greater in tertiary amine TCAs than in secondary amine TCAs?
Anticholinergic effects
Antihistamine effects
Hypotensive effects
Mirtazapine (Remeron)- MOA
Dual neurotransmitter action:
A potent and direct alpha-2 receptor antagonist
Enhances 5-HT and NE transmission
Blocks 5-HT2 and 3 receptors
Results in enhances 5-HT1 reception
Efficacy comparable to standard antidepressants for the treatment of long and short term depression
What is seen less often in mirtazapine as opposed to SSRIs?
Less nausea and less sexual dysfunction
Mirtazapine- Indications
Depression
Comparable efficacy as SSRIS
Mirtazapine- pharmacokinetics
Dosed once daily at bedtime due to sedation
Soltab (dissolvable tablet) used for patients with default swallowing
Mirtazapine- Side effects
- Somnolence (increased risk at lower doses)
- Dry mouth
- Constipation
- Orthostasis
- Increased appetite->weight gain
Venlafaxine (Effexor)- MOA
Inhibits reuptake of NE and 5-HT
Venlafaxine (Effexor)- side effects
Nausea Headache Somnolence Sexual dysfunction Insomnia Agitation Increase in DBP (diastolic blood pressure) (dose related- if needing to increase too much might need to change patient med)
Desvenlafaxine (Pristiq)- MOA
Active metabolite for venlafaxine No mechanistic advantage
SHOULD NOT CHOOSE THIS AS AN EXAM ANSWER
Should pristiq be chosen as a correct answer on the exam?
NO!!!
Duloxetine (Cymbalta)- MOA
Potent 5-HT NE reuptake inhibitor
What else is duloxetine used for besides treating depression?
Urinary incontinence and diabetic neuropathic pain
Duloxetine (Cymbalta)- Side effects
Insomnia/sedation NAUSEA, diarrhea, decreased appetite Sexual dysfunction Sweating Urinary hesitancy Hepatotoxicity- not a huge SE but might want to get AST and ALT Increase in BP
Bupropion (Wellbutrin)- MOA
Believed to block reuptake of dopamine and norepinephrine
What is considered first line agent for depression?
Bupropion along with SSRIs
What else can bupropion be used for?
Smoking cessation
Bupropion (Wellbutrin)- Side effects
-Anxiety, agitation
-Headache
-Seizures– Increased risk with higher doses
sweating
-Tremor
-Insomnia
-GI disturbances (anorexia, nausea, constipation)
-Weight loss
Nefazodone (Serzone)- MOA
Serotonin reuptake inhibitor plus potent 5-HT2 receptor antagonist
Enhanced 5-HT1 neurotransmission through 5-HT2 blockade
Nefazodone (Serzone)- indications
- Comparable efficacy for the treatment of depression as standard antidepressants
- Considered a 2nd or 3rd line agent because of hepatotoxicity risk
- Associated with improvement in symptoms of poor sleep quality, sleep disturbance, anxiety and agitation in depressed patients
Nefazodone (Serzone)- Side effects
Sedation Orthostasis Dry mouth Nausea Increased appetite Blurred vision HEPATOTOXICITY
Trazodone (Desyrel)- MOA
Blocks 5-HT2A receptors (potently); Blocks 5-HT reuptake less potently
Also has antihistaminic properties → Sedation
Monoamine OxidaseInhibitors (MAOIs)- MOA
Block the break down of NE, 5-HT, DA, and epinephrine
What are the MOA-As?
Epinephrine Norepinephrine 5-HT (Serotonin) Dopamine Tyramine
What are the MOA-Bs?
Dopamine
Tyramine
benzylamine
phenylethylamine
**NOT USED FOR DEPRESSION
What are the mixed irreversible MAOIs?
Irreversible: phenelzine, isocarboxazid,
What are the mixed reversible MAOIs?
Reversible: tranylcypromine
Transdermal selegiline
Irreversible inhibitor of MAO-B; inhibits A and B in higher doses (>10 mg/day)
Available as a patch 6 mg, 9 mg, and 12 mg
MAOIs- side effects
Not used as often due to drug-drug and dug-food interactions–Aged, hard cheeses and strongly flavored cheeses contraindicated
SE: orthostasis, dizziness, mydriasis, piloerection, edema, sexual dysfunction, insomnia, weight gain
High risk of serotonin syndrome– Especially when combined with selective serotonin receptor agonists.
High risk of hypertensive crisis
MAOIs- Drug interactions
- Other antidepressant medications, including herbals
- Buspirone
- Meperidine
- Dextromethorphan
- Direct sympathomimetics (e.g., -L-dopa, epinephrine, isoproterenol, norepinephrine)
- Indirect sympathomimetics (e.g., amphetamines, methylphenidate, phenylpropanolamine, ephedra, pseudoephedrine and tyramine)
- Cocaine
What is an adverse effect due to excessive serotonin in the periphery?
Serotonin Syndrome (Toxicity)
What are the sx of serotonin syndrome?
Neuromuscular hyperactivity
Tremor, myoclonus, hyperreflexia, restlessness
Autonomic hyperactivity
Hyperpyrexia, hypertension, tachycardia
Cognitive/behavioral changes
confusion
All antidepressants are considered _______ in efficacy for uncomplicated, unipolar depression?
Equal
Pharmacotherapy choices for depression should be based on what?
Past response to a medication Other psychiatric or medical co-morbidity Potential for drug interaction(s) Safety Patient preference Cost Family member response to a medication
How long does it take for a patient to respond to antidepressents?
Most responders will have an onset of response within 4 weeks
If there is no response to antidepressants by 4 weeks what should happen?
No response at 4 weeks, consider ↑ in dose and waiting another 2-3 weeks
If there is no response or minimal response to antidepressants by 8 weeks what should be done?
Patients showing minimal to no response should not exceed a trial of 8 weeks
Do you need to taper antidepressants?
ALL SSRIS, EXCEPT FLX, SHOULD BE TAPERED BEFORE DISCONTINUATION OR WITHIN CLASS SWITCH
What are the two ways to switch antidepressants?
Can either overlap, taper first drug, and titrate second, or…
Discontinue first drug and start second drug
SSRI- BLACK BOX WARNING
SUICIDE
There may be an increased risk of suicide with SSRIs in children and adolescents
Also an increase in geriatric patients
BUT…
Suicide rates in teens have decreased with increased use of SSRIs
In all clinical trials, no suicide was committed
“Negative” trial does not mean placebo was better
Is it the drug or the disease?
Be cautious and determine risk vs. benefit
What is considered first line for depression for geriatric patients?
SSRIs are considered first-line (tolerability)
NEF, BUP, and VLFX XR also options
TCAs–Generally problematic due to SE profile, DESI and NORT recommended if required
What anti-depressive drugs that should be used in pregnancy/lactation?
SSRIs or TCAs
FLX most studied of the SSRIs
