Antidepressants Flashcards
A 25-year-old woman has a long history of depressive symptoms accompanied by body aches and pain secondary to a car accident 2 years ago. Physical and laboratory tests are unremarkable. Which of the following drugs might be useful in this patient? A. Amitriptyline B. Fluoxetine C. Sertraline D. Phenelzine E. Mirtazapine F. Duloxetine
A. Amitriptyline (TCAD)
F. Duloxetine** *SNRI
SSRIs are much less effective than tricyclic antidepressants in the management of: A. Bulimia B. Chronic pain of neuropathic origin C. Generalized anxiety disorder D. Obsessive-compulsive disorder E. Premenstrual dysphoric disorder
B. Chronic pain of neuropathic origin
Premenstrual depressive disorder (depressive sx during late luteal phase) responses best to
fluoxetine (Serafem)
Describe the monoamine theory of depression
Reserpine depleted brainNE and 5HT –> induced depression
BUT does not totally explain etiology of depression bc white effects on amines are immediate, mood elevating effect is delayed 2-3 weeks
What are adaptations to acute antidepressant tx and chronic antidepressant tx
acute: inhibit 5HT or NE reuptake or breakdown
Chronic: trophic actions, increased fxn and survival of cells via gene alteration
What are examples of SSRIs
- Sertraline (Zoloft)
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
what are examples of SNRIs
- Venlafaxine (Effexor)
2. Duloxetine (cymbalta)
What are examples of TCAD
- amitriptyline (Elavil)
- imipramine
- despramine
What are examples of NDRI
- Bupropion (Wellbutrin)
What class of drugs are the following:
- Trazodone:
- Mirtazapine (Remeron)
- Phenelzine
- Trazodone:5HT partial agonist-SSRI
- Mirtazapine (Remeron): alpha2 antagonists
- Phenelzine: MAOI
Describe the neurodegenerative hypothesis
- Stress causes cortisol release–> detrimental gene transcription response–> neurogenesis inhibited
MOA of TCADs
NE and/or serotonin reuptake inhibitors
MOA of alpha2 antagonists
inhibition of presynaptic a2 autoreceptors that decreases NE release, such a block results in increased NE release
MOA of MAOI
(monoamine oxidase inhibitors)
*block enzyme of major degradation pathway for NE and 5HT in neuron, presumably allowing more presynaptic accumulation and subsequent release into the synapse and again leading to chronic compensatory changes at the synapse
MOA of ECT
increases the amount and activity of the rate limiting enzymes for synthesis of NE (tyrosine hydroxylase) and serotonin (tryptophan hydroxylase) resulting in increased levels of these NT
side effects of SSRIs
ACUTE
- Nausea-diarrhea
- Activation-insomnia
- Restlessness (akathisia)
- Dry mouth
DELAYED:
- Wt. gain
- Sexual dysfunction
- Cognitive blunting
- Very low likelihood of fatallties in OD
- W/D (discontinuation) symptoms–> flu-like
W/D (discontinuation) symptoms w/ SSRIs is related to
half-life (shorter=worse, paroxetine> fluoxetine)
SE of SNRIs
- HTN
- Anxiety
- Nausea
- Dizzy
- Sweating
- Sleepy
- Sexual dysfunction
- more rapid appearance of WD sx than SSRIs
SE of NDRIs
- Dizzy
- Dry mouth
- Tremor
- Insomnia
- Anxiety
- Aggravation of psychosis
- Seizure at HD
SE of Trazodone
- Drowsy- used empirically as hypnotic agent
- Dizzy
- nausea
- agitation
- OD–> minor problems only
SE of Mirtazapine
- Sleepy
- Increased appetite
- Wt. gain
- Dizzy
SE of TCAD
*poor SE profile, declining use, 2nd-3rd line agents
- Sedation (Amitriptyline > Desipramine)
- Antimuscarinic effects (no see, no pee, no spit, no shit) (Amitriptyline > Desipramine)
- Narrow angle glaucoma w/ HD
- Orthostatic hypotension
- Arrhythmias
- Sudden death in OD
- Tremor
- Seizure w/ OD
- Wt. gain (histamine blocking action)
- Sexual disturbances
SE of MOAI
- Postural hypotension via chronic increase in false NT
- Mild anticholinergic effects
- Sedation
- CNS stimulation
- liver damage
- Seizures in OD
- Shock in OD
- hyperthermia in OD
A patient under treatment for a major depressive disorder is brought to the emergency department after ingesting 30 times the normal daily therapeutic dose of imipramine. Which of the following interventions would be least useful?
A. Administer sodium bicarbonate to correct acidosis
B. Administer lidocaine to control cardiac arrhythmias
C. Initiate hemodialysis to hasten drug elimination
D. Maintain heart rhythm by electrical pacing
E. Use intravenous diazepam to control seizures
C. Initiate hemodialysis to hasten drug elimination
Fluoxetine is comparable to the tricyclic antidepressant amitriptyline in:
A. Producing orthostatic hypotension
B. Causing dry mouth and blurred vision
C. Producing life-threatening EKG changes
D. Alleviating the symptoms of depression
E. Causing urinary retention
D. Alleviating the symptoms of depression
Which agent would be a poor choice in a 70-year-old with depressive symptoms due the drug having significant alpha-1 receptor antagonism, thus having a higher risk for falls due to orthostatic hypotension? A. Fluoxetine B. Amitriptyline C. Bupropion D. Escitalopram E. Phenelzine F. Sertraline
B. Amitriptyline (TCAD)
E. Phenelzine (?? causes hypotension via formation of false transmitter NOT via block of a1)
DDI of MAOIs
- Hypertensive crisis w/ decongestants or w/ foods high in tyramine (beer-wine-cheese)–> from acute increase in NE release
A 26-year-old man is receiving pharmacotherapy for a psychiatric disorder. He comes to the emergency room with elevated blood pressure, sweating, headache, and vomiting. His companion tells the physician that the patient became ill at a party where he ate triple-cheese pizza and was drinking Guinness beer. The patient is most likely taking a drug from which therapeutic class?
A. Serotonin selective reuptake inhibitors
B. Tricyclic antidepressants
C. Atypical antipsychotics
D. Monoamine oxidase inhibitors
E. Typical antipsychotics
F. Serotonin norepinephrine reuptake inhibitors
D. Monoamine oxidase inhibitors
DDI of SSRIs + MOAIs
Serotonin syndrome
- hyperthermia
- muscle rigidity
- myoclonus
- Altered mental status
- HTN
- Tachycardia
*Also w/ SSRIs + opiods and antitussives (dextromethorphan)
Which of the following statements concerning the side effects and toxicities of antidepressant drug use is FALSE?
A. Concomitant use of SSRIs and MAOIs may result in a serotonin syndrome.
B. SSRIs (e.g., fluoxetine) can induce hypomania in patients with bipolar disorder.
C. Tricyclic antidepressants (e.g., amitriptyline) have a lower incidence of anticholinergic side effects than SSRIs.
D. Inhibitors of dopamine and norepinephrine reuptake (e.g., bupropion) have been observed to cause anxiety and restlessness due to their mild stimulant action.
E. None of the above
C. Tricyclic antidepressants (e.g., amitriptyline) have a lower incidence of anticholinergic side effects than SSRIs.
To be effective in acute and chronic pain management, tramadol and codeine must be converted to an active form by CYP2D6. Cases of inadequate pain control have occurred when these agents were administered to patients who were being treated with: A. Fluoxetine B. Amitriptyline C. Mirtazapine D. Phenelzine E. Bupropion F. Escitalopram
A. Fluoxetine
DDI of SSRIs
- **inhibition of P450 drug metabolizing enzymes
1. fluoxetine/ paroxetine
2. less concern w/ sertraline and citalopram - can decrease efficacy of drugs requiring activation by CYP2D6 (codeine- tramadol)
**St. John’s Wort- possible induction of P450 drug metabolizing enzymes –> serotonin syndrome in elderly on St. John’s Wort and SSRIs
-Incomplete absorption, significant 1st pass effect
-High protein binding/lipid solubility (high Vd)
-Wide interpatient variations in Cp for a given dose
SSRIs
TCADs
Inhibition is irreversible – continues after drug no longer detectable (2 weeks)
MAOIs
*best to monitor platelet MAOI for determination of duration of MAOI drug effects
A 36-year-old woman presents with symptoms of major depression that are unrelated to a general medical condition, bereavement, or substance abuse. She is not currently taking any prescription or over-the-counter medications. Drug treatment is to be initiated with
sertraline. In your information to the patient, you would tell her:
A. Sertraline may take 2 weeks or longer to become effective
B. It is preferable that she take the drug in the morning
C. Some nausea and GI upset may be present
D. She should notify you if she anticipates using other prescription drugs
A. Sertraline may take 2 weeks or longer to become effective
B. It is preferable that she take the drug in the morning
C. Some nausea and GI upset may be present
D. She should notify you if she anticipates using other prescription drugs
Pros for Bupropion
- Equal efficacy
- Less wt. gain and sexual SE
- not effective in anxious depression
__ is usually the first drug prescribed for depression due to efficacy, tolerability, and once daily dosing
SSRIs
*SNRIs may be more effective but mores SE
A 55-year-old teacher began to experience changes in mood. He was losing interest in his work and lacked the desire to play his daily tennis match. He was preoccupied with feelings of guilt, worthlessness, and hopelessness. In addition to the psychiatric symptoms the patient complained of muscle aches throughout the body. Physical and laboratory tests were unremarkable. After 6 weeks of therapy with fluoxetine, his symptoms resolved. However, the patient complains of sexual dysfunction. Which of the following drugs might be useful in this patient? A. Paroxetine B. Sertraline C. Bupropion D. Citalopram E. Mirtazipine F. Lithium
C. Bupropion
E. Mirtazipine
Most rapid and effective (70-90%) treatment for severe acute depression
- Can be life-saving if patient is suicidal
- Usually 6-12 treatments at a frequency of 2-3 per week
ECT
Adverse effects of ECT
- Cardiopulmonary events
- fx
- orodental injuries
- HA
- Acute contusion
- retrograde and anterograde amnesia
Sexual SE are greatest w/
- SSRIs
- SNRIs
- TCADs
**less w. buproprion
GI SE are greatest w/
- SSRIs (fluoxetine)
- SNRIs (venlafaxine)
*minimize by dividing dose or taking w/ food–> diminshes over time
Wt. gain SE are greatest w/
- Mirtazapine
- paroxetine (SSRI)
*least w/ fluoxetine and bupropion
Serotonin syndrome is most severe w/
SSRI + MAOI (or switched w/o washout period)
Describe the pharmacotherapy used for bipolar
- Mood stabilizer: Lithium or valproate (Depakote)
- Mania: w/ atypical antipsychotics
- Depression: w/ lamotrigine or ADs
- Acute manic sx: Benzos or atypical antipsychotics
Which of the following statements concerning the treatment of bipolar disorder with lithium is accurate (TRUE)?
A. Lithium will alleviate the manic phase of bipolar disorder within 24 hours.
B. Excessive intake of sodium chloride will decrease lithium plasma levels.
C. Lithium dosage may need to be decreased in patients taking thiazide diuretics.
D. Lithium does not cross the blood brain barrier.
E. Lithium does not cross the placental barrier.
F. Lithium is a safe drug with a wide therapeutic index.
B. Excessive intake of sodium chloride will decrease lithium plasma levels.
C. Lithium dosage may need to be decreased in patients taking thiazide diuretics.
MOA of Lithium
- slow onset (10-21 days)
- Use-dependence
- enhance 5HT action and/or diminish NE and DA effect
- interference w/ PIP recyclin g
SE of Lithium
- interference w/ Gs and Gi (adenylyl cyclase) in thyroid and kidney
1. Hypothyroidism/ wt. gain
2. polyuria
3. polydipsia
4. Narrow therapeutic index
5. Fine tremor
6. GI upset
7. muscle weakness
8. MOD: confusion, sedation/lethargy, twitching
9. Severe: seizure, stupor, coma
Describe what can affect Lithium plasma levels
Li plasma increases: Na+ restriction
Li plasma decreases: increase dietary Na+
DDI of Lithium
- diuretics can decrease renal clearance
2. increased Li levels w/ NSAIDs
A 30-year-old male patient is on drug therapy for a psychiatric problem. He complains that he feels “flat” and that he gets confused at times. He has been gaining weight and has lost his sex drive. As he moves his hands, you notice a slight tremor. He tell you that since he has been on this medication he is always thirsty and frequently has to urinate. The drug he is taking is most likely: A. Carbamazepine B. Olanzapine C. Lithium D. Risperidone E. Valproic acid
C. Lithium
A 51-year-old woman with symptoms of major depressive disorder also has angle-closure glaucoma. Which of the following antidepressants should be avoided in this patient? A. Amitriptyline B. Sertraline C. Bupropion D. Mirtazapine E. Imipramine F. Venlafaxine
TCAD!!
A. Amitriptyline
E. Imipramine
A 36-year-old man presents with symptoms of compulsive behavior. If anything is out of order, he feels that “work will not be accomplished effectively of efficiently”. He realizes that his behavior is interfering with his ability to accomplish his daily tasks but cannot seem to stop himself. Which of the following drugs would be most helpful to this patient? A. Imipramine B. Fluoxetine C. Fluvoxamine D. Amitriptyline E. Phenelzine F. Lithium
B. Fluoxetine
C. Fluvoxamine
Regarding the clinical use of antidepressants, which statement is accurate?
A. Chronic use of SSRIs (venlafaxine) increases the activity of hepatic drug-metabolizing enzymes
B. In the treatment of major depressive disorders, citalopram is usually more effective than paroxetine
C. TCADs are highly effective in depressions with attendant anxiety, phobic features, and hypochondriasis
D. Weight gain often occurs during the first few months in patients taking SSRIs
E. When selecting an appropriate drug for treatment of depression, the history of patient response to specific drugs is a valuable guide
E. When selecting an appropriate drug for treatment of depression, the history of patient response to specific drugs is a valuable guide
A recently widowed 76-year-old female patient was treated with a benzodiazepine for several weeks after the death of her husband, but she did not like the daytime sedation it caused even at low dosage. Living independently, she has no major medical problems but appears rather infirm for age and has poor eyesight. Because her depressive symptoms are not abating, you decide on a trial of an antidepressant medication. Which would be the most appropriate choice for this patient? A. Amitriptyline B. Trazodone C. Mirtazapine D. Phenelzine E. Citalopram
E. Citalopram
Uses of SSRI
- Depression
- Generalized anxiety
- Social anxiety
- Panic disorder
- OCD
- PTSD
Uses of SNRIs
- Depression
- Generalized anxiety
- Social anxiety
- OCD
- PTSD
Uses of TCADs
- Depression (2nd line)
- Panic disorder
- Enuresis
- Chronic pain