Psych

Schizophrenia Treatment Goals

• Suppress acute episodes
• Prevent acute exacerbations
• Maintain functioning

First-Generation Antipsychotics

• Block dopamine receptors, causing extrapyramidal symptoms (EPS)
• Examples: chlorpromazine, haloperidol, thioridazine, pimozide
• Adverse Effects (AE):
  • Overdose: hypotension, CNS depression, EPS
  • Tardive dyskinesia (can be irreversible)
  • Dystonia: spasm of tongue, face, neck, or back, oculogyric crisis, opisthotonos
  • Joint dislocation
  • Antipsychotic parkinsonism
  • Akathisia
  • Neuroleptic malignant syndrome (treat with dantrolene and bromocriptine)
• Initial treatment: anticholinergics (benztopine, diphenhydramine)

Haloperidol

• Can be used in children
• AE: galactorrhea, gynecomastia, menstrual irregularities, prolong QT

Second-Generation Antipsychotics

• Block dopamine and serotonin receptors, reducing EPS risk
• AE:
  • Weight gain
  • Diabetes mellitus (DM)
  • Dyslipidemia

Clozapine

• Most effective, improves positive, negative, and cognitive symptoms
• AE:
  • Agranulocytosis (enroll in REMS program, monitor WBC and neutrophil count)
  • Myocarditis (black box warning)
  • Interactions: cancer drugs, phenytoin, ketoconazole

Depot Antipsychotics

• Injectable formulation for long-term therapy
• Lower rate of relapse
• Better for patients with adherence difficulty
• Slow, steady absorption, constant plasma levels between doses
• Dosing: every 2-4 weeks
• Examples: asenapine (SGA, available in sublingual), loxapine (available in 10mg inhaled powder, 1 inhalation/24 hrs)

Treatment Duration

• Continue therapy for at least 12 months after control of an acute episode

Antidepressants

• Depression is caused by the functional insufficiency of monoamine neurotransmitters norepinephrine, serotonin, or both, according to the monoamine deficiency hypothesis.

Classes of Antidepressants

• 5 major classes of antidepressants:
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Atypical antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Examples: citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline
• Do not cause hypotension, sedation, or anticholinergic effects
• Fluoxetine causes CNS excitation rather than sedation
• Adverse effects (AE):
  • Sexual dysfunction (can lower dose or take holidays or add a medication)
  • Weight gain
  • Bruxism, vivid dreams, bleeding disorders, and increased perspiration
  • Birth defects are low
• Serotonin syndrome is possible AE 2-72 hours after treatment, symptoms resolve once the drug is stopped
• Risk of serotonin syndrome if given with MAOIs

Monoamine Oxidase Inhibitors (MAOIs)

• Increases 5-HT availability
• Reserved for patients who have not responded to other medications due to hazards
• Administered orally
• Examples: isocarboxazid, phenelzine, and tranylcypromine
• Can cause hypertensive crisis triggered by foods rich in tyramine
• Do not dispense to those who cannot follow dietary restrictions
• Treatment for hypertensive crisis: vasodilators (nitro, phentolamine, and labetalol)

Selegilin (Transdermal MAOI)

• Bypasses first-pass effect, preserving MAO-A in the intestines, with a low risk with tyramine-rich foods
• Adverse effect: rash
• Contraindications: carbamazepine and oxcarbazepine raise levels of selegilin

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Examples: venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, and milnacipran
• Milnacipran: treats fibromyalgia and sleep
• Duloxetine: off-label for chemo-induced neuropathy and stress urinary incontinence
• Desvenlafaxine: approved for adults, off-label for hot flashes in menopause, and causes weight gain
• Venlafaxine: blocks NE and 5-HT, fetal withdrawal in late pregnancy, and suicide in young

Tricyclic Antidepressants (TCAs)

• Block reuptake of two monoamine transmitters, NE, and serotonin
• Adverse effects:
  • Sedation
  • Orthostatic hypotension
  • Anticholinergic effect
  • Cardiac toxicity
• Lethal if overdose, bicarbonate for dysrhythmias
• Long half-lives, single daily dose
• TCA with MAOI: severe hypertension
• If sedation is warranted: doxepin
• If it's not: desipramine
• Elderly sensitive to anticholinergic effects: nortriptyline

Atypical Antidepressants

• Bupropion:
  • Weight loss
  • Increases sexual desire
  • Can be used with SSRIs
  • Uses: major depressive disorder, prevention of seasonal affective disorder, and stop smoking
  • Adverse effects:
    • Seizures
    • Avoid doses above 450mg/day
    • Rapid dosage titration
    • Patients with seizure risk factors
    • Anorexia and drugs that inhibit CYP (increases bupropion levels)
  • Interactions: sertraline, fluoxetine, paroxentine, and MAOIs
• Mirtazapine:
  • Blocks histamine receptors, promotes sedation and weight gain
  • Adverse effect: somnolence

Postpartum Depression

• Fluoxetine, sertraline, and venlafaxine
• SSRIs are the first choice: tolerated and low risk for toxicity with overdose
• Prevent relapse: treatment should continue at least 6 months
• Sertraline is the safest for breastfeeding
• Brexanolone: first FDA-approved option for PPD, infused over 60 hours in the hospital

Bipolar Disorder Treatment

• Mood stabilizers, antipsychotics, and antidepressants are used to treat bipolar disorder, including bupropion, venlafaxine, and SSRIs (fluoxetine and sertraline).
• Lithium and valproate are preferred, often combined with a 2nd generation (atypical) antipsychotic.

Lithium

• Lithium is the drug of choice for bipolar disorder treatment.
• Monitor blood levels regularly, as it has a short half-life and is excreted daily, requiring divided doses.
• Kidneys excrete lithium, and low sodium levels can cause kidney retention, leading to toxicity.
• Normal sodium intake is essential, and diuretics should be used with caution.
• Plasma levels should be kept between 0.8-1.4 and monitored every 2-3 days initially, then every 3-6 months.
• Levels above 1.5 can cause GI symptoms, hand tremors, confusion, and muscle hyperirritability.
• Levels above 2 can cause seizures, hypotension, coma, and death.
• Lithium can also cause goiter and hypothyroidism.
• Interactions with diuretics, NSAIDs, and anticholinergic drugs can occur due to urinary hesitancy.

Antiepileptic Drugs

• Divalproex, carbamazepine, and lamotrigine are used to treat bipolar disorder.
• Carbamazepine has a trough level of 4-12.
• Lamotrigine is used for long-term maintenance.

Antipsychotics

• Olanzapine, quetiapine, risperidone, aripiprazole, lurasidone, cariprazine, asenapine, and ziprasidone are used to treat bipolar disorder.
• Clozapine can cause agranulocytosis.
• Only aripiprazole, olanzapine, and ziprasidone are approved for long-term use to prevent mood episode recurrence.

Sedatives/Hypnotics

• Barbiturates are schedule III drugs that can cause tolerance and dependence, and are more powerful respiratory depressants that can be fatal in overdose.
• Barbiturates have important applications in seizure and anesthesia, and should be withdrawn slowly.
• Benzodiazepines are the first choice for treating insomnia and anxiety, but can cause confusion and anterograde amnesia.
• Benzodiazepines are weak respiratory depressants, but caution is needed with COPD.
• Alprazolam has a high risk of dependence.

Benzo-like Drugs

• Zolpidem, zaleplon, and eszopiclone are used to treat insomnia.
• Eszopiclone has no limitation on duration of use and can help with sleep maintenance, but has a bitter aftertaste.
• Zaleplon is used for short-term insomnia and helps with falling asleep.
• Zolpidem is used for short-term insomnia and helps with falling asleep and staying asleep.

Ramelteon

• Ramelteon is a new hypnotic that can increase prolactin levels and reduce testosterone levels, leading to amenorrhea, galactorrhea, reduced libido, and fertility problems.
• Fluvoxamine can increase ramelteon levels, and caution is needed with hepatic impairment.

Suvorexant and Lemborexant

• Suvorexant and lemborexant are used to treat chronic insomnia.
• They should not be used with CYP inhibitors (ketoconazole, clarithromycin) or in patients with COPD, OSA, or narcolepsy.
• They can increase digoxin levels.

Trazadone

• Trazadone is an atypical antidepressant with no tolerance.
• Adverse effects include daytime grogginess and postural hypotension.

Anxiety Disorders

• SSRIs and SNRIs are the first-line treatment for generalized anxiety disorder, with only four antidepressants approved: venlafaxine and duloxetine (SNRIs), and paroxetine and escitalopram (SSRIs).
• Benzodiazepines are the first choice for acute anxiety, with examples including alprazolam, lorazepam, chlordiazepoxide, clorazepate, diazepam, and oxazepam.
• Sedation and psychomotor slowing caused by benzodiazepines will subside in 7-10 days.
• Buspirone is an anxiolytic that is not a CNS depressant, has no abuse potential, and does not intensify the effects of other CNS depressants, but its anxiolytic effects are delayed.

Panic Disorder

• SSRIs are the first-line drugs for panic disorder, with examples including fluoxetine, paroxetine, and sertraline.

Obsessive-Compulsive Disorder (OCD)

• SSRIs are the first-line drugs for OCD, with examples including fluoxetine, fluvoxamine, paroxetine, and sertraline.
• TCAs are the second-line treatment, with clomipramine being an example.

Social Anxiety Disorder

• SSRIs are the first-line drugs, with examples including paroxetine and sertraline.
• Benzodiazepines or beta-blockers can also be used for performance anxiety.

Post-Traumatic Stress Disorder (PTSD)

• SSRIs are the first-line drugs, with examples including fluoxetine, paroxetine, and sertraline.
• SNRIs, such as venlafaxine, can also be used.

CNS Stimulants

• Amphetamines are CNS stimulants used to treat ADHD and narcolepsy, and have a 50:50 compound of dextro and levo.
• They release NE and dopamine, and inhibit reuptake, causing peripheral actions of cardiac stimulation and vasoconstriction.
• They have a potential for abuse and side effects including CNS stimulation, weight loss, CV effects, and psychosis.
• Methylphenidate is a CNS stimulant with side effects including insomnia, reduced appetite, emotional lability, and abuse (Schedule II).
• Modafinil is a non-amphetamine stimulant that is absorbed in the GI, and has less abuse potential (Schedule IV).
• Modafinil decreases the effects of birth control and cyclosporine.

Attention Deficit Hyperactivity Disorder (ADHD)

• Stimulants are the first-line treatment, with examples including methylphenidate, dexmethylphenidate, dextroamphetamine, and lisdexamfetamine.
• Side effects of stimulants include insomnia and growth suppression, which can be reduced by taking smaller doses in the afternoon and administering during or after meals.
• Non-stimulant treatments for ADHD include atomoxetine, which is an inhibitor of NE, and guanfacine and clonidine, which are not controlled substances and do not cause anorexia or insomnia.

Drugs with Abuse Potential

Alcohol

• Naltrexone decreases craving for alcohol
• Acamprosate reduces unpleasant feelings brought on by abstinence
• Disulfiram helps to avoid drinking by causing unpleasant effects (acetaldehyde syndrome) if alcohol is ingested, and patients must avoid all forms of alcohol

Smoking

• Medications to help quit:
  • Lozenges
  • Nicoderm and nicotrol patches
  • Nicotine inhaler (not for patients with asthma)
  • Nicotine nasal spray
  • Nicotine gum (AE: mouth and throat soreness)
• Nicotine gum: after 3 months without nicotine, patients should discontinue by tapering
• Other medications:
  • Bupropion
  • Varenicline (AE: CV events; cannot use if truck/bus driver, pilot, or air traffic controllers)

Opioids

• Examples: heroin, oxycodone
• Naloxone is the treatment of choice (autoinjector and nasal spray)
• Medications for maintenance:
  • Opioid agonist (methadone) substituted for those not ready for detox
  • Opioid agonist-antagonist (buprenorphine) substituted for those not ready for detox
• Naltrexone is used for discouragement after detox
• Buprenorphine:
  • Can be prescribed in primary care offices with 8 hours of training and registration with SAMHSA
  • Low potential for abuse, safer than methadone
• Methadone:
  • Suppressive therapy: giving addicts progressively larger doses until 120mg/day
  • AE: prolongs QT and respiratory depression
  • Prescribed in programs

Barbiturates

• Cross-dependency exists between barbiturates and other CNS depressants, but not with opioids
• Phenobarbital can help with withdrawal

Benzodiazepines

• Flumazenil is used for overdose

Methamphetamine

• Treatment: bupropion and modafinil

This quiz covers the goals and treatment of schizophrenia, including the use of conventional antipsychotics, their potency, and potential side effects such as movement disorders and overdose symptoms.