Psychopharmacology

• Psychotropic drugs are used to treat mental disorders
• Categories of these drugs include antipsychotics, antidepressants, mood stabilizers, anxiolytics, and stimulants

Efficacy and Potency

• Efficacy refers to the maximal therapeutic effect a drug can achieve
• Potency is the amount of drug required to produce the maximum effect
• Low-potency drugs require a higher dosage
• High-potency drugs require a low dosage

Half-Life and FDA Role

• Half-life is the time it takes for half of the drug to be removed from the bloodstream
• The Food and Drug Administration (FDA) supervises the testing and marketing of medications to ensure public safety through clinical trials

Off-Label Use and Black Box Warning

• Off-label use refers to using a drug to treat a condition different from what it was originally tested for
• A black box warning indicates serious or life-threatening side effects, and is the most serious warning a medication can have

Principles

• Medication is selected based on its effect on target symptoms
• Effects may take about a month to be fully realized
• Use the lowest effective dose to stabilize target symptoms
• Lower doses are recommended for older adults
• Tapering medications is favored over abrupt cessation to avoid rebound, recurrence of symptoms, or withdrawal
• Follow-up care and a simple regimen increase compliance

Antipsychotic Uses and Mechanism

• Antipsychotics treat symptoms of psychosis, such as delusions and hallucinations
• They are used for schizophrenia, schizophrenia-like disorders, and the manic phase of bipolar disorder
• Off-label uses include treating anxiety, aggressive behavior and disruptive behaviors in Alzheimer's Disease (AD)
• Antipsychotics work by blocking dopamine receptors in the brain

Generations of Antipsychotics

• Conventional or first-generation antipsychotics include chlorpromazine, fluphenazine, thioridazine, haloperidol, and loxapine
• Atypical or second-generation antipsychotics include clozapine, risperidone, and olanzapine
• Third-generation antipsychotics, like aripiprazole, function as dopamine system stabilizers

Conventional vs Atypical vs Dopamine stabilizer

• Conventional antipsychotics are potent dopamine receptor blockers
• Atypical antipsychotics are weak dopamine receptor blockers and serotonin reuptake inhibitors
• Dopamine Stabilizers stabilize dopamine output, increasing it when it is too low and decreasing it when its too high
• Conventional antipsychotics treat positive symptoms with less effect on negative symptoms
• Atypical antipsychotics treat negative symptoms of schizophrenia
• Dopamine Stabilizers can treat both positive and negative symptoms
• Conventional antipsychotics have a high incidence of EPS, where as atypical have lower and stabilizers have less

Extrapyramidal Symptoms

• Extrapyramidal symptoms (EPS) result from dopamine blockage
• Acute dystonia involves muscle rigidity and can cause torticollis, opisthotonus, and oculogyric crisis
• Treatment includes anticholinergic drugs or diphenhydramine
• Pseudoparkinsonism presents with stooped posture, mask-like facies, shuffling gait, cogwheel rigidity, and coarse pill-rolling
• Treatment involves switching to a 2nd/3rd generation antipsychotic or using oral anticholinergics or amantadine
• Akathisia is characterized by restlessness, anxiety, and agitation
• Treatment includes anticholinergics, benzodiazepines, or beta-blockers

Anticholinergic Medications for EPS

• Benztropine is administered 1-3mg BID orally or 1-2mg IM/IV
• Biperiden is administered 2mg TID-QID orally or 2mg IM/IV
• Trihexyphenidyl is administered 2-5mg TID oral

Neuroleptic Malignant Syndrome and Tardive Dyskinesia

• Neuroleptic Malignant Syndrome (NMS) can be fatal and presents with muscle rigidity, high fever, and autonomic instability
• Management involves discontinuing the medication and providing supportive treatment for dehydration and hyperthermia
• Tardive dyskinesia involves permanent involuntary movements
• Symptoms includes tongue thrusting, lip smacking, and grimacing
• Also involves the neck and upper/lower extremities.
• Prevention with Abnormal Involuntary Mvt Scale
• Treatment: Valbenazine (Ingrezza)

Other Antipsychotic Side Effects

• Increased prolactin levels
• Weight gain; more likely with second-generation agents, except ziprasidone
• Metabolic syndrome: High blood pressure, sugar, cholesterol, obesity and greater abdominal girth
• Cardiovascular adverse effects: QT interval prolongation (thioridazine, droperidol, mesoridazine)
• Agranulocytosis (clozapine): Requires weekly WBC count monitoring; must have at least 3500 WBC count before obtaining the next week's supply

Antipsychotic Client Teaching

• Compliance with the medication regimen
• Management of side effects like dry mouth and Thirst(sugar-free candy, fluids), constipation (dietary fiber, exercise) and sleepiness/drowsiness(safety measures)
• If a dose is missed, it should be taken if it is within 4 hours of the usual time

Antidepressant Uses

• Used for major depressive illness, anxiety disorders, depressed phase of bipolar disorder and psychotic depression

Groups of Antidepressants

• Tricyclic and cyclic compounds (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)
• Selective Norepinephrine Reuptake Inhibitor (SNRI)
• Miscellaneous Antidepressant

Mechanisms of Action

• The precise antidepressant mechanism remains not fully understood
• Antidepressants primarily interact with the monoamine neurotransmitter system
• The neurotransmitters affected are serotonin, norepinephrine, and dopamine

Key Points About Different Classes

• SSRIs are first-line drugs for depression due to their rapid effect (2-3 weeks), fewer side effects, and high safety
• SNRIs are newer antidepressants also considered first-line for depression and take effect in 2-4 weeks
• TCAs are used less frequently due to higher frequency of side effects and potentially lethal risk with overdose and take 4-6 weeks to be effective
• MAOIs may cause hypertensive crisis when taking tyramine-rich foods and take 2-4 weeks to be effective

Side Effects

• SSRIs: Anxiety, agitation, akathisia, nausea, insomnia & sexual dysfunction , and weight gain
• Cyclic antidepressants: Anticholinergic effects, orthostatic hypotension, sedation, weight gain, tachycardia and sexual dysfunction
• MAOIs: Daytime sedation, insomnia, weight gain, dry mouth, sexual dysfunction & orthostatic hypotension and hypertensive crisis with foods containing tyramine

Specific Foods to avoid

• Aged cheeses, aged meats, tap beers, sauerkraut, soy sauce, brewer's yeast, yogurt, sour cream

Antidepressant Interactions

• Serotonin Syndrome can occur with MAOI + SSRI
• Symptoms includes Agitation, sweating, fever, tachycardia, hypotension, rigidity, hyperreflexia, Coma and death

Antidepressant Drug Interactions: Treatment

• Muscle relaxants like benzodiazepines
• O2
• IV fluids
• Breathing tube and mech vent
• Beta blocker

Antidepressent - Client Teaching

• Dosing Time: SSRIs should be taken in the morning, cyclic at night
• Missed Doses: Take SSRI up to 8 hours after, cyclic within 3 hours or omit
• Safety measures: Avoid driving

Miscellaneous Antidepressants: Brexanolone and Esketamine

• Brexanolone stands as the first FDA-approved medication for postpartum depression, administered via a 60-minute infusion
• Esketamine effects glutamate by blocking NMDA, is approved for treatment-resistant depression, and defined as two failed antidepressant trials; can only be administered under direct supervision of healthcare provider for nasal spray and is not intended for home use

Mood-Stabilizing Drugs

• Used to treat the highs (manic phase) and lows (depression phase) of bipolar disorder
• mood-stabilizing medications: lithium (Eskalith, Lithobid) and anticonvulsants (carbamazepine, valproic acid, gabapentin, topiramate, oxcarbazepine, and lamotrigine)

Mechanisms of Action

• Lithium normalizes the reuptake of certain neurotransmitters
• Valproic acid and topiramate increase the levels of GABA
• Anticonvulsants stabilize neuron membranes

Lithium Side Effects

• Nausea, diarrhea, anorexia, fine hand tremor, polydipsia, polyuria, metallic taste, fatigue, lethargy, weight gain, acne
• Toxicity includes severe diarrhea, vomiting, drowsiness, muscle weakness, lack of coordination
• Maintain normal salt and fluid intake
• Therapeutic serum lithium level: 1.0mEq/L
• Carbamazepine and valproic acid can cause drowsiness, sedation, dry mouth, and blurred vision

Side Effects of Mood Stabilizers

• Carbamazepine: rash and orthostatic hypotension
• Valproic acid: edema, weight gain, alopecia, and hand tremor
• Topiramate: dizziness, sedation, and weight loss

Adverse Effects of Mood Stabilizers

• Lamotrigine can cause Steven-Johnson Syndrome
• Carbamazepine can cause aplastic anemia and agranulocytosis

Mood-Stabilizing Drugs: Client Teaching

• Periodic monitoring of blood levels, 12 hours after last dose
• Take medication with meals to minimize nausea
• Safety measures if with sedation or dizziness

Antianxiety Drug Uses

• Treatment of anxiety and anxiety disorders, insomnia, obsessive-compulsive disorder (OCD), depression, PTSD, and alcohol withdrawal
• Benzodiazepines and buspirone

Mechanisms of Action

• Benzodiazepines Binds to GABA receptor which reduces cellular excitation leading to a calming effect
• Buspirone acts as a partial agonist at serotonin receptors

Antianxiety Side Effects

• Benzodiazepines: Physical and psychological dependence & Central nervous system (CNS) depression
• Must be avoided with CNS depressants Alcohol, and tolerance of sedation
• Buspirone: Dizziness, sedation, nausea, and headache, and does not cause physical dependence

Other Drugs Used for Anxiety

• Symptoms, neurotransmitters, and circuits associated with anxiety/depressive disorders overlap extensively
• First-line treatment options include
  • Benzodiazepine – fast onset; misuse potential
  • Antidepressant – slow onset; but long term effect; the preferred choice for long-term treatment

Client Teaching for Anti-Anxiety

• Safety measures if there is sedation and avoidance of alcohol
• One drink while on a benzodiazepine may have the effect of three drinks
• Avoid abrupt discontinuation
• Benzodiazepine withdrawal can be fatal

Stimulant Uses and Medications

• Used for ADHD in children and adolescents, residual attention-deficit disorder in adults and narcolepsy.
• Medication includes Amphetamines; methylphenidate, amphetamine, and dextroamphetamine
• Non-stimulant medication: Atomoxetine (Strattera) – SNRI -Pemoline (Cylert) – infrequently used d/t liver failure

Mechanism and Dosage

• Causes a release of norepinephrine, dopamine, and serotonin presynaptically
• Dosage divided; higher doses for narcolepsy in adults
• Doses for treating ADHD vary widely (based on age, weight, and behavior of children)

Side Effects and Client Teaching for Stimulents

• Anorexia, weight loss, nausea and irritability
• Growth and weight suppression (long term effect)
• Can be prevented by taking drug holidays during weekends and holidays
• Dose after meals to minimize nausea and anorexia
• Avoidance of caffeine, sugar and chocolate
• Proper storage out of reach of children

Disulfiram

• Used as Aversion therapy for alcoholism
• Works by inhibiting the enzyme involved with alcohol metabolism
• Adverse reaction with alcohol ingestion; Facial and body flushing, throbbing headache, vomiting, dizziness Severe Symptoms: chest pain, severe hypotension, dyspnea, death
• Side effects: fatigue, drowsiness, halitosis, tremor, impotence
• Interacts with phenytoin, barbiturates, long-acting benzodiazepines
• Teach Patient avoidance of alcohol found in common products (e.g., shaving cream, deodorant, and over-the-counter cough preparations) with a alcohol free label

Acamprosate

• Prescribed for persons in recovery from alcohol abuse or dependence
• Works by reducing the physical and emotional discomfort during the first weeks/months of sobriety
• Persons with renal impairment cannot take these medications