Exam 4 Flashcards
What are the general considerations for schizophrenia and the drug therapy of schizophrenia?
Schizophrenia - most debilitating of psychotic disorders. It affects 1% of population. The onset is typically 15-20 years old.
- Antipsychotic, neuroleptic, and anti-schizophrenic are all synonymous
Positive symptoms - respond well to drug therapy. Ex. hallucinations, delusions, etc.
Negative symptoms - little response to drug therapy. Ex. blunted emotion, poor self care, social withdrawal, etc.
*also decrease in cognitive function
Which neutrotransmitters are thought to be involved with schizophrenia? (Hypotheses)
α1, D2, 5HT2A, M1,3, H1 receptors are all targeted by therapies. The effectiveness of targeting each receptor varies by patient.
Serotonin -
- LSD and mescaline are 5HT agonists, which cause hallucinations
- 5HT2A receptors modulate dopamine release in the cortex, limbic region, and striatum
- 5HT2A receptors modulate glutamate release and NMDA receptors
Glutamate
- Excitatory
- Phencyclidine and ketamine are noncompetitive inhibitors of NMDA receptors that exacerbate psychosis and cognition
- GlyT inhibitors and Glu agonists are effective in schizophrenia
Dopamine
- D2 receptors highly involved
- Dopaminergic agents exacerbate symptoms of schizophrenia
- D2 receptor antagonists initially increase metabolites in the CNS, then later decrease metabolites
- D2 antagonists - want to target the mesolimbic system, risk of motor effects and EPS
When do drug-induced movements occur, what target is responsible, which drugs are likely to cause them, and how can they be treated?
Extrapyramidal Symptoms (EPS) - Occurs in 30-50% of patients
- Occurs in the early days/weeks of treatment
- Reversible!!
- Symptoms: dystonia (increased muscle tone), pseudoparkinsonism (muscle rigidity), tremor, akathisia (restlessness)
- Target responsible: D2 antagonist causes DA/ACh to be off
- Treatment: Anticholinergics, antihistamines, DA releasing agent, propranolol (for akathisia)
Tardive Dyskinesia - Occurs in 20-40% of patients
- Occurs late months/year
- IRREVERSIBLE
- Symptoms: rhythmic involuntary movements with mouth, irregular jerking movements (choreiform), athetoid (worm-like) movements, axial hyperkinesias (to and fro)
- Target responsible: Unclear. Maybe supersensitivity of receptors to dopamine?
- Treatment: Need to PREVENT. Monitor and use lowest possible doses; Reduce doses, change drug, eliminate anticholinergics; VMAT inhibitors (indirectly blocks dopamine release)
Neuroleptic Malignant Syndrome (NMS) -
- Serious and rapid; 10% fatality
- Symptoms: EPS with fever, impaired cognition, muscle rigidity
- Treatment: Restore dopamine balance; D/c drug, used DA agonists, diazepam, or dantrolene (skeletal muscle relaxant)
What are the adverse pharmacological effects associated with antipsychotic drugs? (autonomic, CNS, endocrine system, other)
autonomic -
- anticholinergics: loss of accomodation, dry mouth, difficulty urinating, constipation
- α adrenoceptor blockade: orthostatic hypotension, impotence, failure to ejaculate
CNS -
- DA receptor blockade: parkinson’s syndrome, akathasia, dystonias
- Supersensitivity of DA receptors: tardive dyskinesia
- Muscarinic blockade: toxic-confusional state
- H1 receptor blockade: sedation
Endocrine -
- DA receptor blockage resulting in hyperprolactinemia: amenorrhea-galactorrhea, infertility, impotence
Other -
- H1 + 5HT2C blockade: Weight gain
What are some precautions and contraindications for antipsychotic drugs?
Cardiovascular (most will prolong the QTc interval)
Parkinson’s Disease
Epilepsy (clozapine will lower seizure threshold)
Diabetes (for newer agents)
What does it mean to have a high or low 5-HT2A/D2 ratio? Which drugs have a high or low 5-HT2A/D2 ratio?
High - mostly binding D2 (not 5HT2A); High D2 blockade is associated with extrapyramidal symptoms (dystonia, pseudoparkinsonism, tremor, akathisia)
Low - binds similarly to both receptors (D2 and 5HT2A)
Drugs with very high: thiothixene
Drugs with very low: clozapine, risperidone, quetiapine
What are the pharmacological target, action, and side effects of Chlorpromazine, Promethazine, and Thioridazine?
1st gen antipsychotics - strong D2 blocks, which can cause more movement problems (EPS & TD)
Chlorpromazine (Thorazine) - is the 1st antipsychotic, has antihistamine side effects
Promethazine (Phenergan) - has antihistamine side effects and is an antiemetic
Thioridazine (Mellaril) - can cause many side effects, such as sedation, hypotension, anticholinergic side effects, sexual dysfunction, cardiovascular, etc.
What are the pharmacological target, action, and side effects of Fluphenazine, Prochlorperazine, and Perphenazine?
1st gen antipsychotics - strong D2 blocks, which can cause more movement problems (EPS & TD)
Fluphenazine (Permitil, Prolixin) - lots of EPS
Prochlorperazine (Compazine) - Antiemetic
Perphenazine (Trilafon) - has similar efficacy, less weight gain, and is cheaper than several of the newer agents when used with anticholinergic
What are the pharmacological target, action, and side effects of Thiothixene, Haloperidol, Molindone, and Pimozide?
1st gen antipsychotics - strong D2 blocks, which can cause more movement problems (EPS & TD)
Thiothixene (Navene) - Has modest EPS
Haloperidol (Haldol) - EPS
Molidone (Moban) - Has moderate EPS
Pimozide (Orap) - Used for Tourette’s disease to suppress motor and vocal tics
What are the pharmacological target, action, and side effects of Clozapine, Olanzapine, and Loxapine?
atypical/2nd gen antipsychotics - Reduced EPS, enhanced 5HT2A receptor antagonism, more metabolic problems
Clozapine (Clozaril) - 1st atypical, very effective; Has anticholinergic and antihistamine side effects, can cause agranulocytosis, increases diabetes risk
Olanzapine (Zyprexa) - Causes weight gain, less likely to cause N/V, less likely to cause movement disorders, increases diabetes risk
Loxapine (Loxitane) - Older agent. The parent agent is an antipsychotic, but its metabolite is an antidepressant (useful with psychosis + depression)
What are the pharmacological target, action, and side effects of Quetiapine, Risperidone, Paliperidone, Iloperidone?
atypical/2nd gen antipsychotics - Reduced EPS, enhanced 5HT2A receptor antagonism, more metabolic problems
Quetiapine (Seroquel) - Has 5HT2A + D2. Has low antimuscarinic properties, low EPS, can cause hypotension and sedation, increases diabetes risk
Risperidone (Risperidol) - Designed to be 5HT2A and D2 antagonist, relatively low EPS at <8mg/day, causes weight gain and some sedation
Paliperidone (Invega) - Add hydroxyl group on 9th carbon of risperidone
Iloperidone (Fanapt) - Structurally related to risperidone, very potent at α1 receptors
What are the pharmacological target, action, and side effects of Ziprasidone, Asenapine, Lurasidone, Pimavanserin?
atypical/2nd gen antipsychotics - Reduced EPS, enhanced 5HT2A receptor antagonism, more metabolic problems
Ziprasidone (Geodon/Zeldox) - 5HT2A. D2, α1 affinity, prolongs QT interval
Asenapine (Saphris) - 5HT2A and D2 (also α and histamine receptors)
Lurasidone (Latuda) - 5HT2A, D2. Less weight gain and metabolic effects compared to olanzapine, fast onset, higher doses don’t usually increase effectiveness, rapid titration
Pimavanserin (Nuplazid) - Inverse agonist on 5HT2A, used for Parkinson’s disease psychosis since it doesn’t bind D2
What are the pharmacological target, action, and side effects of Aripiprazole, Brexpiprazole, Cariprazine, Lumateperone?
Aripriprazole (Abilify) - atypical, high affinity for 5HT2A and D2, causes weight gain and has low risk of D2 effects because it has partial agonist activity
Brexpiprazole (Rexulti) - D2/D3 partial agonist with less akathisia than aripiprazole. Used for schizophrenia and as an adjunct to antidepressants
Cariprazine (Vraylar) - D2/D3 partial agonist with greater affinity to D3. Has a lot of akathisia. Used for schizophrenia, mania, and bipolar disorder
Lumateperone (Caplyta) - partial D2 agonist and 5HT2A antagonist
What are the key structural features of the phenothiazine antipsychotics?
- 3 rings
- R2 is important for potency (ex. Cl, CF3, SCH3)
- R10 requires a 3 atom chain to bind to the receptor
What are the adverse pharmacological effects associated with antipsychotic drugs? (autonomic, CNS, endocrine system, other)
autonomic -
- anticholinergics: loss of accomodation, dry mouth, difficulty urinating, constipation
- α adrenoceptor blockade: orthostatic hypotension, impotence, failure to ejaculate
CNS -
- DA receptor blockade: parkinson’s syndrome, akathasia, dystonias
- Supersensitivity of DA receptors: tardive dyskinesia
- Muscarinic blockade: toxic-confusional state
- H1 receptor blockade: sedation
Endocrine -
- DA receptor blockage resulting in hyperprolactinemia: amenorrhea-galactorrhea, infertility, impotence
Other -
- H1 + 5HT2C blockade: Weight gain
What the key features that define psychotic disorders?
Positive symptoms:
- Delusions: fixed, false beliefs that are not changed even with conflicting evidence
- Hallucinations: Perception-like experiences that occur without an external stimulus (usually auditory, also visual, tactile, or olfactory)
- Disorganized thinking and speech: switching from one topic to another, unrelated answers to questions
- Disorganized or abnormal motor behavior
Negative symptoms: losing interest in motivations and relationships, etc.
When do men and women usually develop schizophrenia?
Men - late teens/early 20s (this is earlier than women by 5-10 years)
Women - late 20s/early 30s (estrogen is protective)
What does smoking have to do with schizophrenia? What effect can marijuana, cocaine, and amphetamine use have on schizophrenia?
Smoking - more than 75% of people with schizophrenia use tobacco
- Smoking induces 1A2 due to hydrocarbons that are produced and inhaled. This DECREASES serum concentration of 1A2 substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)!!!!!
Marijuana, cocaine, and amphetamine can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse
*important to treat substance use with schizophrenia
What is the most commonly used typical antipsychotic? What important side effect is more common with the typicals? How do the typicals affect positive and negative symptoms of schizophrenia?
Haloperidol is most commonly used, whether thats PRN or maintenance; Also given as a long-acting injection q4 weeks
EPS is common with the higher potency typicals
Typical antipsychotics are great for treating positive symptoms, but are likely to worsen negative symptoms and cognitive symptoms
What are the clinical pearls for these atypical antipsychotics: Clozapine (+REMS requirements), Iloperidone, Lumateperone, Lurasidone, and Olanzapine
Clozapine - the MOST EFFECTIVE antipsychotic, requires REMS monitoring due to agranulocytosis, may cause cardiomyopathy, hypersalivation, hypotension, metabolic syndrome, and dose-related seizures. Is a 1A2 substrate
- REMS: monitor ANC weekly x 6 months, biweekly x 6 months, then q4 weeks.
Iloperidone - boxed warning for QTc prolongation, causes orthostatic hypotension. Is a 2D6 and 3A4 substrate.
Lumateperone - Is a D1/D2 partial agonist. Take with food to enhance absorption. Is a UGT and 3A4 substrate.
Lurasidone - MUST take with food to improve bioavailability. Higher risk of akathisia, lower risk of weight gain/metabolic syndrome. Is a 3A4 substrate.
Olanzapine - high risk of sedation, weight gain, hyperglycemia, hyperlipidemia, metabolic syndrome, anticholinergic effects at high doses. Is a 1A2 substrate.
- REMS
What are the clinical pearls for these atypical antipsychotics: Paliperidone, quetiapine, risperidone, ziprasidone
Paliperidone - ER dosage can come out as a ghost tablet. Renally eliminated, so dose adjust in renal impairment, higher risk of EPS and hyperprolactinemia, moderate weight gain/metabolic syndrome
Quetiapine - boxed warning for QTc prolongation, risk of sedation, moderate weight gain/metabolic syndrome. Is a 3A4 substrate
Risperidone - Higher risk of EPS and hyperprolactinemia, moderate risk of weight gain/metabolic syndrome. Is a 2D6 substrate (produces paliperidone)
Ziprasidone - MUST be taken with food for bioavailability, lower risk of weight gain/metabolic syndrome and akathisia. No P450 metabolism
How do you use the Asenapine transdermal patch (Secuado)? What are the warning and metabolism interactions?
Apply one patch every 24 hours, rotate patch site to minimize application site reactions.
Has a warning for QTc prolongation
UGT and 1A2 substrate (reduce the dose of the patch if it’s given with strong 1A2 inhibitors (ex. fluvoxamine))
Which medication is approved for the treatment of hallucinations/delusions in a patient with Parkinson’s? What is its MOA and what is its metabolism interactions?
Pimavanserin
- MOA: inverse agonist and antagonist at the serotonin 5HT2A receptor (not DA)
- 3A4 substrate
What is Samidorphan used for? What’s its MOA?
Samidorphan is used to mitigate the weight gain and metabolic syndrome of olanzapine (given as olanzapine/samidorphan)
- MOA: opioid antagonist with preferential activity at the mu opioid receptor
What must be done with Risperdal Consta when initiating treatment? What kind of injection is Perseris and what metabolism interactions does it have?
Risperdal Consta (IM injection) - It MUST be supplemented with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment. Until the 3rd injection, which is week 4.
Perseris - LAI of risperidone, abdominal SQ injection; 3A4 substrate, use 120mg dose if 3A4 inducer or may need oral supplementation.
How do you initiate Invega Sustenna and how is it eliminated? How do you initiate Invega Trinza and at what CrCL is it not recommended? When can you initiate Invega Hafyera and where is the injection?
Invega Sustenna - paliperidone (IM)
- Initiation: loading dose, then booster, then injection q4 weeks starting 5 weeks after the loading injection.
*the initial loading dose and booster dose must be given in the deltoid to improve absorption consistency
**if loading strategy was followed, we don’t need oral antipsychotic overlap
- renally eliminated, so may require dose adjustment in moderate to severe renal impairment
Invega Trinza - paliperidone (IM)
- Initiation: Can be initated for a pt who has been on a stable monthly IM injection of Invega Sustenna for at least 4 doses; This is a q3mo IM injection
*recommended to be given in deltoid, gluteal lowers Cmax
- Not recommended in CrCL < 50mL/min
Invega Hafyera - paliperidone (IM - gluteal)
- Can be initiated after 4 months of Invega Sustenna or one 3 month dose of Invega Trinza
*gluteal injection ONLY
What is a serious side effect of Zyprexa Relprevv?
Zyprexa Relprevv - Olanzapine injection
- PDSS: post-dose delirium sedation syndrome
- on REMS program due to similar side effect of olanzapine (high risk of sedation, weight gain, hyperglycemia, hyperlipidemia, metabolic syndrome, anticholinergic effects at high doses)
How can you initiate Abilify Maintena and where is it to be injected? When do you need to make dosage adjustments for Abilify Maintena?
Abilify Maintena - aripiprazole injection
- MUST overlap with oral aripiprazole (or other oral antipsychotic) for at least 14 days after the first injection
- Deltoid or gluteal injection
- Dosage adjuments: If taking 2D6 inhibitor or 3A4 inhibitor or inducer for more than 14 days as concomitant therapy (lower dose with inhibitors, don’t use with inducers)
How can you initiate Aristada?
Aristada - aripiprazole lauroxil (prodrug)
- overlap with oral aripiprazole for 3 weeks after the first injection
What do we use for psychiatric emergencies? (immediate release antipsychotic injections)
- Haloperidol, chlorpromazine, fluphenazine are used, but haloperidol is used most commonly
- Olanzapine IR IM CANNOT be given at the same time as benzodiazepine IR injection due to boxed warning for respiratory depression!!
- Loxapine for inhalation is not commonly used due to REMS
What are the 4 manifestations of EPS and how do we treat them?
acute dystonia - muscle group reaction that is not life-threatening, but very frightening. Give IM anticholinergic NOW dose (ex. benztropine 2mg, diphenhydramine 50mg)
drug-induced parkinson’s - oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)
akathisia - feeling of restlessness, increases risk for suicidal thinking/behaviors. Use beta-blocker (propranolol is 1st line), benzodiazepine (usually lorazepam)
tardive dyskinesia - VMAT inhibitors
What VMAT inhibitors can we use and what are the important side effects and metabolism interactions?
tetrabenazine - not FDA approved for TD, boxed warning for suicidality/depression, causes QTc prolongation
valbenazine - FDA approved, causes QTc prolongation, 2D6 and 3A4 substrate
deutetrabenazine - FDA approved, causes QTc prolongation, 2D6 substrate
What is neuroleptic malignant syndrome?
Neuroleptic malignant syndrome - life-threatening medical emergency that is caused by the effects of antipsychotics on dopamine blockade. Symptoms include hyperpyrexia, tachycardia, labile blood pressure, muscle rigidity, significantly elevated CK, myoglobinuria
Treatment is supportive, d/c antipsychotics, consider DA agonists
Future antipsychotic use is NOT contraindicated (you can even use the same drug, but likely switch to another antipsychotic)
What are the adverse effects of metabolic syndrome? Which agents have the most/least risk of this?
metabolic adverse effects - hyperglycemia, hyperlipidemia, hypertension, etc.
Most - clozapine & olanzapine
Mid - quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexpiprazole
Least - Ziprasidone & Lurasidone & Aripiprazole
When do we monitor personal/family hx, weight, waist circumference, blood pressure, A1c, and fasting lipids for metabolic monitoring?
personal/family hx - at baseline & yearly
weight - baseline and q4 weeks-q3 months
waist circumference - baseline & yearly
BP - baseline, q3 months & yearly
A1c - baseline, q3 months & yearly
fasting lipids - baseline, q3 months, q5 years
What are important warnings for all antipsychotics?
- Boxed Warning: increased risk of death in elderly pts treated with antipsychotics for dementia w/ related behaviors
- Metabolic adverse effects
- EPS
- Risk of somnolence, postural hypotension, and motor/sensory instability increases fall risk
*fall risk assessment should be performed for pts at higher risk of falling
What are the general considerations for depression? What’s the basis behind the individual hypotheses? (biogenic amine, neurodendocrine, neurotropic)
clinical features - when the physiological symptoms (decreased sleep, appeptite changes, fatigue, etc) and psychological symptoms (dysphoric mood, worthlessness, excessive guilt) and cognitive symptoms (decreased concentration, suicidal ideation) get so severe that they interfere with your life
biogenic amine hypothesis - due to depletion of NE and 5HT. We’ve seen that reserpine, which causes depletion of NE and 5HT from vesicles causes depresison. We also know that agents that increase 5HT and NE treat depression. Also mutations in the SERT, NET, and DAT (minor) transporters can affect depression. Additionally, alterations in 5HT1A/2C and α2 receptors
neuroendocrine hypothesis - overactivity of HPA and elevated CRF is found in almost all depressed pts and can lead to other negative effects. Antidepressants and ECT reduce CRF levels
neurotropic hypothesis - decreased BDNF is related to depression. Decreased volume of the hippocampus is also involved (regulates HPA + memory). Loss of BDNF = less dendritic sprouts for neurological processes
How are the individual hypothesis of depression integrated with each other? Esp. involving BDNF and HPA axis
- HPA and steroid abnormalities regulate BDNF levels (more BDNF is good, overactivity of HPA is bad)
- During stress, hippocampal glucocorticoid receptors are activated by cortisol, which results in a decrease in BDNF
- BDNF is increased with chronic activation of monoamine receptors for over 2 weeks
- Chronic activation of monoamine receptors also downregulates HPA axis
What are the proposed MOAs associated with these antidepressants: MAOIs, TCAs, SSRIs, SNRIs
MAOIs - Block the breakdown of NE and 5HT by monoamine oxidase (MAO), thus increasing their concentration in the synapse
- non-selective MAO inhibitors (irreversible): phenelzine, tranylcypromine
- MAO-B selective (reversible): selegiline
- MAO-A selective (reversible): moclobemine
TCAs -
- tertiary amines inhibits NE and 5HT reuptake through NET and SERT (also muscarinic, histamine, and adrenergic antagonists); Ex. imipramine, amitrytyline (both of these have active metabolites), doxepin, clomipramine
- secondary amines are more selective for NE than 5HT; Ex. desipramine, nortriptyline, protriptyline, and maprotiline; These cause less side effects
SSRIs - Blocks reuptake of 5HT through SERT, which allows serotonin to stay in the synapse for longer
- fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram
SNRIs - NET & SERT inhibitors
- venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran
What are the proposed MOAs associated with these antidepressants: 5-HT2 antagonists, tetracyclic and unicyclic antidepressants, NSRIs
5-HT2 antagonists -
- trazodone is a 5HT2a antgonist and weak SERT inhibitor. Almost always used for sleep, not depression
tetracyclic and unicyclic antidepressants -
- Maprotiline is a NET inhibitor (4º)
- Mirtazapine is an α2 antagonist, 5HT2/T3 antagonist, and H1 antagonist (4º)
- Bupropion is a DAT inhibitor, NET/SERT inhibitor (1º)
NSRIs - norepinephrine selective reuptake inhibitors; These are very similar to secondary amine TCAs, but have less side effects
- reboxetine (can’t be used in the US)
- atomoxetine (not approved for depression, used for ADHD)
Which receptors are associated with the side effects of antidepressants?
MAOIs - headache, drowsiness, dry mouth, weight gain, orthostatic hypotension, sexual dysfunction
*avoid foods with tyramine
TCAs - QTc prolongation (extremely dangerous), sedation, anticholinergic, autonomic effects, weight gain
- secondary amines have a better side effect profile than the tertiary amines
SSRIs - N/V, headache, sexual dysfunction, anxiety, insomnia, tremor (these are all pretty modest), serotonin syndrome risk
*avoid abrupt d/c
SNRIs
5-HT2 antagonists
tetracyclic and unicyclic antidepressants
What newer antidepressants (dual/multiple actions or rapidly acting) may have advantages or different applications compared to the other agents?
SSRI + HT1A partial agonists - vilazodone (Viibryd), vorioxetine (Brintellex)
- these have reduced sexual side effects vs. pure SSRIs, but as a whole are pretty similar to the SSRIs
NMDA antagonists - ketamine at subanesthetic doses, esketamine (intanasal, REMS); These are rapid acting
How does Brexanolone work for post-partum depression?
allopregnanolone levels are increased during pregnancy. It’s thought that GABA-A receptors may desensitize during this. Postpartum, allopregnanolone levels return the normal. Brexanolone resensitizes these GABA-A receptors.
How does filbanserin (addyi) work?
Filbanserin - agonist at 5HT1A, antagonist at 5HT2A/C
- used for hypoactive sexual desire disorder, but it was developed as an antidepressant
- selective at prefrontal cortex
*controversial approval
What are the major structural differences between MAOIs, TCAs, and SSRIs?
MAOIs - one ring with carbon chain
TCAs - 3 ring structure
SSRIs - don’t look like a 3 ring connected structure. Usually has at least one-two aromatic rings
What therapeutic agents are available for the treatment of mania/bipolar disorder and what are their important side effects and when do they occur?
lithium - very dirt drug. Mechanism is not clearly understood, but involves depletion of PIP2 & its associated signaling. Also modulate GSK2.
- SE:
anticonvulsants -
- valproate increases GABAergic tone, block Na+ channels, block T-type Ca2+ channels, inhibits histone deacetylase (HDAC5)
- carbamazepine/oxcarbazepine work on Na+ channels
- lamotrigine works on Na+ and Ca+
- topiramate works on Na+ and may enhance GABA
atypical antipsychotics - these are dirty drugs (but not as dirty as lithium)
- olanzapine, quetiapine, risperidone, ziprasidone, lurasidone, aripiprazole
What are the risk factors for depression? What does SIGECAPS represent? What are risk factors for suicide?
Risk factors for depression - feelings of guilt, chronic fatigue/headache, sleep disturbances, loss of sexual interest, agitation, anxiety, hopelessness
S - sleep (too much or not enough)
I - interest (loss of interest in things they used to like)
G - guilt (excessive guilt)
E - energy (not enough)
C - concentration (unable to stay concentrated)
A - appetite (over/under)
P - psychomotor (move slower, no motivation to keep moving)
S - suicide
Risk factors for suicide - have a detailed plan, anniversary or loss, widowed/unmarried, substance misuse, increasing age, unemployment, gender (more women when younger, more white men when older), living alone, physical or mental illness, family history, lack of social support, PRIOR ATTEMPTS
What are the two diagnostic criteria for depression?
- depressed mood most of the day nearly every day
- markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
What medications can contribute to depression symptoms?
- beta blockers
- hormonal therapy
- isotretinoin
- CNS depressants
- interferon-beta
- levetiracetam
- atomoxetine
- indomethacin
What are the natural products for depression? What metabolism interactions are there?
- St. John’s wort: CYP450 3A4 inducer, causes photo toxicity
- SAMe (S-adenoxyl-L-methionine)
These two agents can also increase the risk of serotonin syndrome, leading to severe N/D, dizziness, headache, agitation, tachycardia, hallucinations
what is the step-wise approach to treatment of depression?
Week 1 - better appetite
Week 2 - better sleep/energy
*in weeks 1/2, anxiety will be increased, so anxiolytics may be needed
Week 4 - better mood
Week 6 - increased mood (the goal is absence of symptoms)
Months 2-3 - efficacy can be properly assessed
Months 4-9 - continuous phase (goal is to eliminate residual symptoms/prevent relapse)
Months 12-36 - (goal is to prevent the recurrence of depression)
What warning do all antidepressants have for patients age 24 or younger?
Increased risk of suicidal thinking and behavior
*there’s actually a protective factor for ages ≥65 years old
**medguides are required for all antidepressants
