Psychopharm Flashcards
What are HAM side effects?
What drugs cause HAM side effects?
Antihistamine (sedation, weight gain)
Antiadrenergic (orthostatic hypotension, cardiac abnormalities, sexual dysfunction)
Antimuscarinic (dry mouth, blurred vision, urinary retention, constipation, exacerbation of neurocognitive disorders [eg dementia], precipitation of narrow-angle glaucoma)
Found in TCAs and low-potency antipsychotics (eg chlorpromazine [thorazine], thioridazine [mellaril])
Characteristics of serotonin syndrome
Confusion, flushing, diaphoresis, tremor, myoclonic jerks, hyperthermia, hypertonicity, rhabdomyolysis, renal failure, death
- Occurs when there is too much serotonin, classically when SSRIs and MAOIs are combined.
- As this combo is rarely seen in practice anymore, serotonin syndrome is more commonly seen when a patient is prescribed multiple medications with serotonergic activity (eg SSRIs/SNRIs, trazodone, Tramadol, triptans, dextromethorphan, St. Johns wort, ondansetron)
- Tx: stop meds, supportive care
Hypertensive crisis
Caused by buildup of stored catecholamines, triggered by combination of MAOIs with tyramine-rich foods (eg red wine, cheese, chicken liver, cured meats) or with sympathomimetics.
Extrapyramidal side effects
Parkinsonism - masklike face, cogwheel rigidity, bradykinesia, pill-rolling tremor
Akathisia - restlessness, need to move, agitation
Dystonia - sustained, painful contractions of muscles of neck, tongue, eyes, diaphragm
- Occur more frequently with high-potency, typical (first gen) antipsychotics (eg Haldol, prolixin, stelaine, orap), but can be seen with atypical
- Reversible
- occur within hours to days
In rare cases, can be life-threatening (eg dystonia of diaphragm)
Hyperprolactinemia
Occurs with high-potency, typical first gen antipsychotics and risperidone.
Tardive dyskinesia
Choreoatetoid muscle movements, usually of mouth and tongue (can affect extremities as well)
- Occurs after years of antipsychotic use (more likely with high-potency, first-generation)
- Usually irreversible
Neuroleptic malignant syndrome
Mental status changes, fever, tachycardia, HTN, tremor, elevated creatine phosphokinase (CPK), “lead pipe” rigidity
- Can be caused by any antipsychotic after short or long time (increased with high-potency, typical antipsychotics)
- Medical emergency with up to 20% mortality rate
CYP450 inducers
Tobacco (1A2)
Carbamazepine (1A2, 2C9, 3A4)
Barbiturates (2C9)
St. John’s wort (2C19, 3A4)
CYP450 inhibitors
Fluvoxamine (1A2, 2C19, 3A4) Fluoxetine (2C19, 2C9, 2D6) Paroxetine (2D6) Duloxetine (2D6) Sertraline (2D6)
List of SSRIs
Fluoxetine (Prozac) Sertraline (Zoloft) Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro)
Fluoxetine (Prozac)
SSRI
- longest half life, with active metabolites
- no need to taper
- safe in pregnancy, approved for use in children and adolescents
- common side effects: insomnia, anxiety, sexual dysfunction)
- can elevate levels of antipsychotics, leading to increased effects
Sertraline (Zoloft)
SSRI
- higher risk for GI disturbances
- very few drug interactions
- other common side effects: insomnia, anxiety, sexual dysfunction
Paroxetine (Paxil)
SSRI
- potent inhibitor of CYP26, which can lead to several drug-drug interactions
- common side effects: anticholinergic effects eg sedation, constipation, weight gain) and sexual dysfunction
- short half-life leading wo withdrawal phenomena if not taken consistently
Fluvoxamine (Luvox)
SSRI
- Currently approved only for use in OCD
- Common side effects: nausea and vomiting
- Multiple drug interactions due to CYP inhibition
Citalopram (Celexa)
SSRI
- Fewest drug-drug interactions
- Dose-dependent QTc prolongation
Escitalopram (Lexapro)
SSRI
- Levo-enantiomer of citalopram; similar efficacy, possibly fewer side effects
- Dose dependent QTc prolongation
How to address the sexual side effects of SSRIs
Sexual side effects of SSRIs can be treated by either reducing the dose (if clinically appropriate), changing to a non-SSRI antidepressant, augmenting the regimen with bupropion, or, in men, by adding meds like sildenafil
SSRI most associated with weight gain?
Most weight-neutral SSRIs?
weight gain: Paxil
weight neutral: fluoxetine and sertraline
Side effects of SSRIs
Common, resolving within a few days:
- GI disturbance (nausea and diarrhea; giving with food can help)
- Insomnia; also vivid dreams, often resoles over time
- Headache
- Weight changes (either up or down)
Other side effects:
- Sexual dysfunction (30-40%): decreased libido, anorgasmia, delayed ejaculation. These may occur weeks to months after taking an SSRI and typically do not resolve
- Restlessness: akathisia-like state
- Serotonin syndrome: Caused by excess of serotonin in body. Can result form a single agent or multiple agents in combo (eg triptans used with SSRIs)
- Hyponatremia (rare)
- Seizures: rate of approximately 0.2%, slightly lower than TCAs
SNRIs
Venlafaxine (Effexor)
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
SNRI
- Often used for depressive disorders, anxiety disorders (like GAD), and neuropathic pain
- low drug interaction potential
- Etended release form allows for once-daily dosing
- Side effect profile similar to SSRIs, with the exception of increased BP in higher doses. Do not use in patients with untreated or labile BP
- New form, desvenlafaxine (Pristiq) is the active metabolite of venlafaxine; expensive and no known benefit over venlafaxine
Duloxetine (Cymbalta)
SNRI
- Often used for people with depression, neuropathic pain, and in fibromyalgia
- Side effects similar to SSRIs, but more dry mouth and constipation relating to neuroepinephrine effects
- Hepatotoxicity may be more likely in patients with liver disease or in heavy alcohol use, so LFTs should be monitored as indicated.
Bupropion (Wellbutrin)
NE-DA reuptake inhibitor
Lack of sexual side effects
Some efficacy in treatment of adult ADHD
Effective for smoking cessation
Weight neutral
Side effects include increased anxiety, as well as increased risk of seizures and psychosis at high doses
Contraindicated in patients with epilepsy or active eating disorders and in those currently on an MAOI. Use with caution with agents that also lower seizure threshold (stimulants)
Serotonin Receptor Antagonists and Agonists
Trazodone (Desyrel) and Nefazodone (Serzone)
- Useful in treatment of major depression, major depression with anxiety, and insomnia (secondary to sedative effects)
- Do not have sexual side effects of SSRIs and do not affect REM sleep
- Side effects: nausea, dizziness, orthostatic hypotension, cardiac arrhythmias, sedation, priapism (especially trazodone)
- Due to orthostatic hypotension at higher doses, trazodone is not frequently used as an antidepressant. Commonly used to treat insomnia when initiating an SSRI (until insomnia improves as the depression resolves)
- Nefazodone carries a black box warning for rare but serious liver failure (1 per 250,000-300,000 people) and is rarely used
Alpha-2 adrenergic receptor antagonists
Mirtazapine (Remeron)
- Useful in treatment of major depression, especially in patients who have significant weight loss or insomnia
- Side effects include sedation, weight gain, dizziness, tremor, dry mouth, constipation, and (rarely) agranulocytosis.
- Fewer sexual side effects compared to SSRIs and few drug interactions
- Helpful for treating major depression in the elderly - helps with sleep and appetite
Heterocyclic antidepressants: types and subtypes
Tricyclics (TCAs) - inhibit reuptake of NE and 5HT
- long half lives, dosed once daily
- rarely used as first-line agents due to side effects and lethality in overdose
- Tertiary amines: (high degree of HAM side effects):
1. Amitriptyline (Elavil)
2. Imipramine (Tofranil)
3. Clomipramine (Anafranil)
4. Doxepin (Sinequan) - Secondary amines: (metabolites of tertiary amines [less HAM]
1. Nortriptyline (Pamelor, Aventyl)
2. Desipramine (Norpramin)
- Tertiary amines: (high degree of HAM side effects):
Tetracyclics
1. Amoxapine
Amitriptyline (Elavil)
Tricyclic tertiary amine
Useful in chronic pain, migraines, insomnia
Imipramine (Tofranil)
Tricyclic tertiary amine
- Has IM form
- Useful in enuresis and panic disorder
Clomipramine (Anafranil)
Tricyclic tertiary amine
Most serotonin-specific, therefore useful in treatment of OCD
Doxepin (Sinequan)
Tricyclic tertiary amine
- Useful in treating chronic pain
- Emerging use as a sleep aid in low doses
Nortriptyline (Pamelor, Aventyl)
Tricyclic secondary amine
- Least likely to cause orthostatic hypotension
- Useful therapeutic blood levels
- Useful in treating chronic pain
Desipramine (Norpramin)
Tricyclic secondary amine
- More activating/less sedating
- Least anticholinergic
Amoxapine (Asendin)
Tetracyclic antidepressant
- Metabolite of antipsychotic loxapine
- May cause EPS and has a similar side-effect profile to typical antipsychotics
Side effects of TCAs
- Highly protein-bound and lipid soluble, therfore can interact with other meds that have high protein binding
- Antihistaminergic: sedation and weight gain
Antiadrenergic: CV - orthostatic hypotension, dizziness, reflex tachy, arrhythmias (block cardiac Na channels), ECG changes (widening QRS, QT, PR intervals). Avoid in patients with preexisting conduction abnormalities or recent MI** - Antimuscarinic (anticholinergic): Dry mouth, constipation, urinary retention, blurred vision, tachycardia,exacerbation of narrow angle glaucoma
- Lethal in overdose
- OD symptoms: agitation, tremors, ataxia, arrhythmias, delirium, hypoventilation from CNS depression, myoclonus, hyperreflexia, seizures, coma
- Seizures: risk is direct related to dose and serum level
- Serotonergic effects: Erectile/ejaculatory dysfunction in males, anorgasmia in females
Treatment of TCA overdose
Sodium bicarbonate
properties of MAO-Is
- Prevent inactivation of biogenic amines such as NE, 5HT, DA, tyramine
- Irreversibly inhibit MAO-A and MAO-B
- MAO-A preferentially deactivates serotonin and NE, and MAO-B preferentially deactivates phenethylamine, both types also act on DA and tyramine
- Not typically first line due to increased safety/tolerability of newer agents; can be used for refractory depression
MAOIs
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Isocarboxazid (Marplan)
Selegeline (Emsam transdermal patch) - does not require following dietary restrictions when used in low dosages but still must avoid decongestants, opiates (such as meperidine, fentanyl, tramadol) and serotonergic drugs)
Side effects of MAOIs
- Serotonin syndrome occurs when SSRIs and MAOIs are taken together or if other drugs cause increases in serotonin levels **wait at least 2 weeks before switching from SSRI to MAOI and at least 5-6 weeks with fluoxetine
- Hypertensive crisis (risk when MAOIs are taken with tyramine-rich foods or sympathomimetics)
- Foods with tyramine (red wine, cheese, chicken liver, fava beans, cured meats) cause a buildup of stored catecholamines
- In addition to markedly elevated BP, it is also characterized by HA, sweating, n/v, photophobia, autonomic instability, CP, arrhythmia, death
- Foods with tyramine (red wine, cheese, chicken liver, fava beans, cured meats) cause a buildup of stored catecholamines
- Orthosatic hypotension (most common)**
- Drowsiness
- Weight gain
- Sexual dysfunction
- Dry mouth
- Sleep dysfunction
- Patients with pyridoxine deficiency can have numbness or paresthesias, so they should supplement with B6**
- Liver toxicity, seizures, edema (rare)
- “start low and go slow”
Antidepressant use in other disorders
OCD: SSRIs (high doses), TCAs (clomipramine)
Panic disorder: SSRIs, SNRIs, TCAs, MAOIs
Eating disorders: SSRIs (in high doses), TCAs
Persistent depressive disorder (dysthymia): SSRIs, SNRIs (eg venlafaxine, duloxetine)
Social anxiety disorder (social phobia): SSRIs, SNRIs, MAOIs
GAD: SSRIs, SNRIs (venlafaxine), TCAs
PTSD: SSRIs
IBS: SSRIs, TCAs
Enuresis: TCAs (imipramine)
Neuropathic pain: (TCAs (amitriptyline and nortriptyline), SNRIs
Chronic pain: SNRIs, TCAs
Fibromyalgia: SNRIs
Migraine: TCAs (amitriptyline)
Smoking cessation: Bupropion
PMDD: SSRIs
Insomnia: Mirtazapine, trazodone, TCAs (doxepin)
Parkinson’s: selegiline (MAO-B inhibitor)
Treatment of serotonin syndrome
First discontinue the med
Then provide supportive care and benzos
Serotonin antagonist cyproheptadine can also be used
Mechanisms of typical vs atypical antipsychotics
Typical: block dopamine D2
Atypical: block Serotonin 5HT2A
Efficacy of typical vs atypical antipsychotics on positive and negative symptoms
Positive symptoms - atypical and typical have similar efficacy
Negative symptoms - atypical antipsychotics may be more effective
Types of typical antipsychotics
Low-potency:
- Chlorpromazine (thorazine)
- Thioridazine (Mellaril)
Mid-potency:
- Loxapine (Loxitane)
- Thiothixene (Navane)
- Molindone (Moban)
- Perphenazine (Trilafon)
High-potency:
- Haloperidol (Haldol)
- Fluphenazine (Prolixin)
- Trifluoperazine (Stelazine)
- Pimozide (Orap)
Characteristics of low-potency, typical antipsychotics
- Lower affinity for dopamine receptors and therefore higher dose is required.
- Higher incidence of HAM side effects compared to high-potency
- Lower incidence of EPS and (possibly) neuroleptic malignant syndrome
- More lethality in OD due to QTc prolongation and potential for heart block and v-tach
- Rare risk for agranulocytosis and slightly higher seizure risk than high-potency
Drugs: Chlorpromazine (Thorazine)
Thioridazine (Mellaril)
Chlorpromazine (Thorazine)
Low-potency, typical antipsychotic
- Commonly causes orthostatic hypotension
- Can cause blue-gray skin discoloration as well as corneal and lens deposits
- Can lead to photosensitivity
- Also used to treat nausea and vomiting, as well as intractable hiccups
Thioridazine (Mellaril)
Low-potency, typical antipsychotic
- associated with retinitis pigmentosa
Loxapine (Loxitane)
Mid-potency, typical antipsychotic
- higher risk of seizures
- metabolite is an antidepressant
Thiothixene (Navane)
Mid-potency, typical antipsychotic
- can cause ocular pigment changes
Properties of high-potency, typical antipsychotics
- Greater affinity for dopamine receptors, therefore a relatively low dose is needed to achieve effect
- Less sedation, orthostatic hypotension, anticholinergic effects (less HAM)
- Greater risk for EPS and (likely) TD
Drugs: Haloperidol (Haldol), Fluphenazine (Prolixin), Trifluoperazine (Stelazine), Pimozide (Orap)
Haloperidol (Haldol)
High-potency, typical antipsychotic
- Can be given PO/IM/IV. Decanoate (long-acting) form available
Fluphenazine (Prolixin)
High-potency, typical antipsychotic
- Decanoate form available
Trifluoperazine (Stelazine)
High-potency, typical antipsychotic
- Approved for nonpsychotic anxiety
Pimozide (Orap)
High-potency, typical antipsychotic
- A/w QTc prolongation and v-tach
Mechanisms of major antipsychotic side effects
targeting of positive symptoms, EPS, prolactin increase
- Positive symptoms of schizophrenia are treated by the action of the medications in the mesolimbic dopamine pathway. The mesolimbic pathway includes the nucleus accumbens, the fornix, the amygdala, and the hippocampus
- The negative symptoms of schizophrenia are thought to occur due to decreased dopaminergic action in the mesocortical pathway
- EPS occur through blockade of the dopamine pathways in the nigrostriatum
- Increased prolactin is caused by dopamine blockade in the tuberoinfundibular area
Extrapyramidal symptoms
Parkinsonism - bradykinesia, masklike face, cogwheel rigidity, pill-rolling tremor
Akathisia - subjective anxiety and restlessness, objective fidgetiness. Patients may report a sensation of inability to sit still. Best treated with beta blockers or benzos.
Dystonia - sustained painful contraction of muscles of neck (torticollis), tongue, eyes (oculogyric crisis). Can be life-threatening if it involves airway or diaphragm.
Hyperprolactinemia
Leads to decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea
List of antipsychotic side effects
Antidopaminergic: EPS including Parkinsonism, akathisia, dystonia; hyperprolactinemia Anti-HAM effects Tardive dyskinesia Neuroleptic malignant syndrome Elevated liver enzymes, jaundice Ophthalmologic problems Dermatologic problems Seizures
Tardive dyskinesia
Choreoathetoid (writhing) movements of mouth and tongue (or other body parts) that may occur in patients who have used neuroleptics for more than 6 months.
- Older age is a risk factor
- Women and patients with affective disorders may be at increased risk
- Although 50% of cases will remit (without further antipsychotic use) most cases are permanent
- Treatment involves discontinuation of current antipsychotic if clinically possible and changing to a medication with less potential to cause TD
Neuroleptic malignant syndrome
- Rare, occurs more often in young males early in treatment with high-potency antipsychotics.
- Medical emergency with up to 20% mortality rate if left untreated.
- Characterized by:
Fever (most common presenting symptom)
Autonomic instability (tachycardia, labile hypertension, diaphoresis)
Leukocytosis
Tremor
Elevated CPK
Rigidity (lead pipe rigidity is considered almost universal)
Excessive sweating
Delirium (mental status changes) - Treatment involves discontinuation of current medications and administration of supportive medical care (hydration, cooling, etc)
- Sodium dantrolene, bromocriptine, and amantadine may be used but have their own side effects with unclear efficacy.
- This is not an allergic reaction
- Patient is not prevented from restarting the same neuroleptic at a later time, but will have an increased risk for another episode of neuroleptic malignant syndrome
Ophthalmologic problems a/w antipsychotics
Irreversible retinal pigmentation with high doses of thioridazine, deposits in lens with chlorpromazine.
Dermatologic problems a/w antipsychotics
Rashes and photosensitivity (blue-gray skin discoloration with chlorpromazine)
Seizures a/w antipsychotic use
All antipsychotics lower the seizure threshold, although low-potency antipsychotics are more likely.
Properties of atypical (second generation) antipsychotics
- Block both dopamine and serotonin receptors and are associated with different side effects than typical antipsychotics
- Less likely to cause EPS, TD, or neuroleptic malignant syndrome
- May be more effective in treating negative symptoms of schizophrenia than typical
- Atypical antipsychotics are also used to treat acute mania, bipolar disorder, and as adjunctive meds in unipolar depression
- Also used in treating borderline personality disorder, PTSD, and certain psychiatric disorders in childhood (eg tic disorders)
Drugs: Clozapine (Clozaril) Risperidone (Risperdal) Quetiapine (Seroquel) Olanzapine (Zyprexa) Ziprasidone (Geodon) Aripiprazole (Abilify) Paliperidone (Invega) Asenapine (Saphris) Iloperidone (Fanapt) Lurasidone (Latuda)
List of atyipcal antipsychotics
Clozapine (Clozaril) Risperidone (Risperdal) Quetiapine (Seroquel) Olanzapine (Zyprexa) Ziprasidone (Geodon) Aripiprazole (Abilify) Paliperidone (Invega) Asenapine (Saphris) Iloperidone (Fanapt) Lurasidone (Latuda)
Onset of antipsychotic side effects:
NMS, acute dystonia, Parkinsonism/Akathisia, Tardive dyskinesia
NMS: any time (but usually early in treatment)
Acute dystonia: hours to days
Parkinsoism/Akathisia: days to weeks
Tardive dyskinesia: months to years
Clozapine (Clozaril)
Atypical antipsychotic
- Less likely to cause tardive dyskinesia
- Only antipsychotic shown to be more efficacious than the others; used in treatment refractory schizophrenia *
- More anticholinergic side effects than other atypical or high-potency typical antipsychotics: a/w tachycardia and hypersalivation
- Risk of severe side effects:
- 1% incidence of agranulocytosis; clozapine must be stopped if the absolute neutrophil count drops below 1500 per microliter
- 4% incidence of seizures
- small risk of myocarditis
Risperidone (Risperdal)
Atypical antipsychotic
- Can cause increased prolactin
- A/w orthostatic hypotension and reflex tachycardia
- Long-acting injectable form named Consta
Quetiapine (Seroquel)
Atypical antipsychotic
- Much less likely to cause EPS; common side effects include sedation and orthostatic hypotension
Olanzapine (Zyprexa)
Atypical antipsychotic
- Common side effects include weight gain, sedation, and dyslipidemia
Ziprasidone (Geodon)
Atypical antipsychotic
- Less likely to cause significant weight gain, a/w QTc prolongation, and must be taken with food (50% reduction in absorption without a 300 calorie meal)
Aripiprazole (Abilify)
- Unique mechanism: partial D2 agonism
- Can be more activating (akathisia) and less sedating
- Less potential for weight gain
Newer (more expensive) Atypical antipsychotics
Paliperidone (Invega):
- Metabolite of risperidone
- long-acting injectable form (Sustenna)
Asenapine (Saphris): orally dissolving sublingual tablet
Iloperidone (Fanapt)
Lurasidone (Latuda): must be taken with food, used in bipolar depression
Side effects of atypical antipsychotics
Metabolic syndrome
- Must be monitored with baseline weight, waist circumference (measured at iliac crest), BP, HbA1c, fasting lipids
- Weight gain: metformin can be used to reduce or prevent
- Hyperlipidemia
- Hyperglycemia - rarely diabetic ketoacidosis has been reported
Some anti-HAM effects
Elevated LFTs - monitor yearly for elevation in LFTs and ammonia
QTc prolongation
Mood stabilizers overview - indications
Used to treat acute mania and to help prevent relapse of manic episodes (maintenance treatment) in bipolar disorder and schizoaffective disorder. Less commonly they may be used for:
- Augmentation of antidepressants in patients with major depression refractory to monotherapy
- Potentiation of antipsychotics in patients with schizophrenia or schizoaffective disorder
- Treatment of aggression and impulsivity (eg neurocognitive disorders, intellectual disability, personality disorders, other medical conditions)
- Enhancement of abstinence in treatment of alcoholism.
Drugs: include lithium and anticonvulsants, most commonly valproic acid, lamotrigine, and carbamazepine
Antipsychotics used in the treatment of acute mania
Quetiapine Olanzapine Aripiprazole Risperidone Asenapine Ziprasidone
All have FDA approval for treatment of mania
Mood stabilizer that can decrease suicidality
Lithium (only one that does this)
Lithium - properties
- Drug of choice in acute mania and as ppx for both manic and depressive episodes in bipolar and schizoaffective disorders
- Also used in cyclothymic disorder and unipolar depression
- Metabolized by kidney, so dosing adjustment may be necessary in patients with renal disease
- Prior to initiating, patients should have ECG, basic chemistries, thyroid function tests, CBC, and pregnancy test
- Onset of action takes 5-7 days
- Blood levels correlate with clinical efficacy and should be checked 4-5 days after every dose change
- Major drawback of lithium is its high incidence of side effects and very narrow therapeutic index:
- Therapeutic range: 0.6-1.2 (individual patients can have significant side effects even within this range)
- Toxic: >1.5
- Potentially lethal: > 2.0
Psych meds where blood levels are useful
Lithium, valproic acid, carbamazepine, clozapine
Side effects of lithium
- AMS, coarse tremors, convulsions, delirium, coma, death
- Clinicians need to monitor blood levels of lithium, TFT, and kidney function
- Fine tremor
- Nephrogenic DI
- GI disturbance
- Weight gain
- Sedation
- Thyroid enlargement, hypothyroidism
- ECG changes
- Benign leukocytosis
- May cause Ebstein’s anomaly
Factors that increase Li+ levels
- NSAIDs
- Aspirin (+/-)
- Thiazide diuretics
- Dehydration
- Salt deprivation
- Sweating (salt loss)
- Impaired renal function
Carbamazepine (Tegretol)
Anticonvulsant
- Especially useful in treating mania with mixed features and rapid cycling bipolar disorder; less effective for the depressed phase
- Acts by blocking sodium channels and inhibiting action potentials
- Onset of action is 5-7 days
- Must check pregnancy test prior to initiating therapy as it increases the risk of neural tube defects
- Carries risk of rash, SIADH, hyponatremia, benign leukopenia, and aplastic anemia (rare)
- CBC, LFTs, must be obtained before initiating treatment and regularly monitored during treatment
- Carbamazepine auto-induces its own metabolism. Patients may therefore need a dose increase in the first few weeks to months
- Serum carbamazepine levels should be measured initially and at 3,6, and 9 weeks. Goal level is 4-12 mcg/mL
Side effects of carbamazepine (Tegretol)
- Most common are GI and CNS (eg drowsiness, ataxia, sedation, confusion)
- Possible skin rash (Stevens-Johnson syndrome)
- Leukopenia, hyponatremia, aplastic anemia, thrombocytopenia, and agranulocytosis
- Elevation of liver enzymes causing hepatitis
- Teratogenic effects when used during pregnancy (neural tube defects)
- Significant drug interactions with many medications metabolized by the cytochrome P450 pathway, including inducing its own metabolism through autoinduction (requiring increasing dosages)
- Toxicity: confusion, stupor, motor restlessness, ataxia, tremor, nystagmus, twitching, and vomiting
Valproic acid (Depakote and Depakene)
Mood stabilizer/anticonvulsant
- Useful in treating acute mania, mania with mixed features, and rapid cycling
- Multiple mechanisms of action: blocks sodium channels and increases GABA concentrations in the brain
- Monitoring LFTs and CBC is necessary
- Drug levels should be checked after 4-5 days. Therapeutic range is 50-150 ug/mL
- Contraindicated in pregnancy, so care should be given in women of childbearing age
List of anticonvulsants
Carbamazepine (Tegretol) Valproic acid (Depakote and Depakene) Oxcarbazepine (Trileptal) Gabapentin (Neurontin) Pregabalin (Lyrica) Tiagabine (Gabitril) Topiramate (Topamax)
Lamotrigine (Lamictal)
Anticonvulsant
- Efficacy for bipolar depression, though little efficacy for acute mania or prevention of mania
- Believed to work on sodium channels that modulate glutamate and aspartate
- Most common side effects are dizziness, sedation, headaches, and ataxia
- Most serious side effect is Stevens-Johnson syndrome (life-threatening rash involving skin and mucous membranes) in 0.1%. This is most likely in the first 2-8 weeks, but is minimized by starting with low doses and increasing slowly.
- Valproate will increase lamotrigine levels, and lamotrigine will decrease valproate levels
Oxcarbazepine (Trileptal)
Anticonvulsant
- As effective in mood disorders as carbamazepine, but better tolerated
- Less risk of rash and hepatic toxicity
- Monitor sodium levels for hyponatremia
Gabapentin (Neurontin)
Anticonvulsant
- Often used adjunctively to help with anxiety, sleep, neuropathic pain
- Little efficacy in bipolar disorder
Pregabalin (Lyrica)
Anticonvulsant
- Used in GAD (second line) and fibromyalgia
- Little efficacy in bipolar disorder
Tiagabine (Gabitril)
Anticonvulsant
- Questionable benefit in treating anxiety
Topiramate (Topamax)
Anticonvulsant
- May be helpful with impulse control disorders
- Beneficial side effect is weight loss
- Can cause hypochloremic, metabolic acidosis as well as kidney stones
- The most limiting side effect is cognitive slowing
Side effects of anticonvulsants
GI symptoms Weight gain Sedation Alopecia Pancreatitis Hepatotoxicity or benign aminotransferase elevations Increase in ammonia Thrombocytopenia Teratogenic effects during pregnancy (neural tube defects
Properties of anxiolytics/hypnotics and general properties
Include benzodiazepines, barbiturates, and buspirone Common indications for anxiolytics/hypnotics include: - Anxiety disorders - Muscle spasm - Seizures - Sleep disorders - Alcohol withdrawal - Anesthesia indution
Benzodiazepines - general properties
- Most widely prescribed psychotropic medications
- Potentiate the effects of GABA
- Reduce anxiety and can be used to treat akathisia
- Many patients become physically dependent and tolerant
- Potential for abuse
- Choice of BDZ is based on time to onset of action duration of action, and method of metabolism
- Relatively safer in overdose than barbiturates
Long-acting benzos (half life > 20 h)
Diazepam (Valium)
Clonazepam (Klonopin)
Intermediate-Acting benzos (half life: 6-20 hours)
- Alprazolam (Xanax)
- Lorazepam (Ativan)
- Oxazepam (Serax)
- Temazepam (Restoril)
Short acting benzos (half life < 6 hours)
- Midazolam (Versed)
Diazepam (Valium)
Long-acting benzo
- Rapid onset
- Used during detox from alcohol or sedative-hypnotic anxiolytics, and for seizures
- Effective for muscle spasm
- Less commonly prescribed to treat anxiety because of euphoria
Clonazepam (Klonopin)
Long acting benzo
- Treatment of anxiety, including panic attacks
- Avoid with renal dysfunction: longer half-life allows for once or twice daily dosing
Alprazolam (Xanax)
Intermediate-acting benzo
- Treatment of anxiety, including panic attacks
- Short onset of action leads to euphoria, high abuse potential
Lorazepam (Ativan)
Intermediate acting benzo
- Treatment of panic attacks, alcohol and sedative-hypnotic anxiolytic detox, agitation
- Not metabolized by the liver
Oxazepam (Serax)
Intermediate acting benzo
- Alcohol and sedative-hypnotic anxiolytic detoxification
- Not metabolized by liver
Temazepam (Restoril)
Intermediate acting benzo
- Because of dependence, rarely used for treatment of insomnia
- Not metabolized by liver
Midazolam (Versed)
Short acting benzo
- very short half life
- primarily used in medical and surgical settings
Side effects of benzos
Drowsiness
Impariment of intellectual function
Reduced motor coordination (Careful in elderly)
Anterograde amnesia
Withdrawal can be life-threatening and cause seizures
Toxicity: respiratory depressino in overdose, especially when combined with alcohol
Non-benzo hypnotics
Zolpidem (Ambien)/Zaleplon (Sonata)/Eszopiclone (Lunesta)
Diphenhydramine (Benadryl)
Ramelteon (Rozerem)
Zolpidem (Ambien)/Zaleplon (Sonata)/Eszopiclone (Lunesta)
Non benzo hypnotics
- Work by selective receptor binding to the omega-1 receptor on the GABA-A receptor, which is responsible for dsedation
- Should be used for short-term treatment of insomnia
- Compared to benzos, less tolerance/dependence occurs with prolonged use
- Zaleplon has shorter half life than zolpidem, which has a shorter half-life than eszopiclone
- Reports of anterograde amnesia, hallucinations, parasomnias (sleepwalking), and GI side effects may limit their tolerability
Diphenhydramine (Benadryl)
Non benzo hypnotic
- Antihistamine with moderate anticholinergic effects
- Side effects include sedation, dry mouth, constipation, urinary retention, blurry vision
Ramelteon (Rozerem)
Non benzo hypnotic
- Selective melatonin MT1 and MT2 agonist
- No tolerance or dependence
Non benzo anxiolytics
Buspirone (BuSpar)
Hydroxyzine (Atarax)
Barbiturates (eg butalbitol, phenobarbital, amobarbitol, pentobarbital)
Propranolol
Buspirone (BuSpar)
non benzo anxiolytic
- Partial agonist at 5HT-1A receptor, thereby decreasing serotonergic activity
- Slower onset of action than benzos (takes several weeks for effet)
- Not considered as effective as other options, and so it is often used in combination with another agent (eg ssri) for treatment of GAD
- Does not potentiate the CNS depression of alcohol (useful in alcoholics) and has a low potential for abuse/addiction
Hydroxyzine (Atarax)
Non-benzo anxiolytic
- An antihistamine
- Side effects include sedation, dry mouth, constipation, urinary retention, and blurry vision
- Useful for patients who want quick acting, short term medication but who cannot take benzos for various reasons
Barbiturates (eg butalbitol, phenobarbital, amobarbitol, pentobarbital)
Non-benzo anxiolytic
- Rarely used because of the lethality of overdose, potential for abuse, and side-effect profile
Propranolol
Non-benzo anxiolytic
- Beta blocker
- Useful in treating the autonomic effects of panic attacks or social phobia (ie performance anxiety), such as palpitations, sweating, tachycardia
- It can also be used to treat akathisia (side effect of antipsychotics)
Psychostimulants
Used in ADHD and treatment-refractory depression
Dextroamphetamine and amphetamines (Dexedrine, Adderall)
Methylphenidate (Ritalin, Concerta)
Atomoxetine (Strattera)
Modafinil (Provigil)
Destroamphetamine and amphetamines (Dexedrine, Adderall)
Psychostimulants
- Dextroamphetamine is the D-isomer of amphetamine
- Schedule II due to high potential for abuse/diversion
- Monitor BP and watch for weight loss, insomnia, exacerbation of tics, decreased seizure threshold
Methylphenidate (Ritalin, Concerta)
Psychostimulants
- CNS stimulant, similar to amphetamine
- Schedule II
- Watch for leukopenia or anemia
- Monitor BP and CBC with differential, and watch for weight loss, insomnia, exacerbation of tics, decreased seizure threshold
Atomoxetine (Strattera)
Psychostimulants
- Inhibits presynaptic norepinephrine reuptake, resulting in increased synaptic norepinephrine and dopamine
- Less appetite suppression and insomnia
- Not classified as a controlled substance
- Less abuse potential than dextroamphetamine/methylphenidate but less effetive
- Rare liver toxicity, and possible increase in suicidal ideation in children/adolescents
Modafinil (Provigil)
Psychostimulant
- Used in narcolepsy, not ADHD
Cognitive enhancers
Used in major neurocognitive disorders Acetylcholinesterase inhibitors: - Donepezil (Aricept) - Galantamine (Razadyne) - Rivastigmine (Exelon)
NMDA (glutamate) receptor antagonist
- Memantine (Namenda)
Donepezil (Aricept)
Acetylcholinesterase inhibitor
- Once daily dosing
- Some GI side effects
- Used in mild-to-moderate neurocognitive disorders (dementias)
Galantamine (Razadyne)
Acetylcholinesterase inhibitor
- Twice-daily dosing
- GI side effects
- Used in mild-to-moderate neurocognitive disorders (dementias)
Rivastigmine (Exelon)
Acetylcholinesterase inhibitor
- Twice-daily dosing
- Has daily patch form, with fewer side effects
- Used in mild-to-moderate neurocognitive disorders (dementias)
Memantine (Namenda)
NMDA (glutamate) receptor antagonist
- Used in moderate-to-severe neurocognitive disorders (dementia)
- Fewer side effects than cholinesterase inhibitors
- Should be used in conjunction with acetylcholinesterase inhibitor
Drugs that may cause psychosis
Sympathomimetics, analgesics, antibiotics (eg isoniazid, antimalarials), anticholinergics, anticonvulsants, antihistamines, corticosteroids, antiparkinsnian agents
Drugs that may cause agitation/confusion/delirium
Antipsychotics, anticholinergics, antihistamines, antidepressants, antiarrhythmics, antineoplastics, corticosteroids, NSAIDs, antiasthmatics, antibiotics, antihypertensives, antiparkinsonian agents, thyroid hormones
Drugs that may cause depression
Antihypertensives, antiparkinsonian agents, corticosteroids, calcium channel blockers, NSAIDs, antibiotics, peptic ulcer drugs
Drugs that may cause anxiety
Sympathomimentics, antiasthmatics, antiparkinsonian agents, hypoglycemic agents, NSAIDs, thyroid hormones
Drugs that may cause sedation/poor concentration
Antianxiety agents/hypnotics, anticholinergics, mood stabilizers, antibiotics, antihistamines, antipsychotics (eg clozapine, quetiapine olanzapine)
Selected meds and their psych side effects
Procainamide, quinidine: confusion, delirium
Albuterol: Anxiety, confusion
Isoniazid: Psychosis
Tetracycline: Depression
CImetidine: Depression, confusion, psychosis
Steroids: Aggressiveness, agitaiton, mania depression, anxiety, psychosis
