Psycho Pharm Medium

• These study notes cover psychotherapeutic drugs, focusing on depression and bipolar disorder treatments, including antidepressants, mood stabilizers, antipsychotics, and their mechanisms, precautions, and adverse effects.

Depression: Clinical Manifestation and Etiology

• Depression manifests emotionally as persistent sadness, hopelessness, anhedonia, worthlessness, guilt, and dejection.
• Cognitive manifestations include difficulty concentrating, indecisiveness, and recurrent thoughts of death or suicide.
• Physical manifestations involve changes in sleep (insomnia/hypersomnia), anorexia, weight loss (or hyperphagia/weight gain), fatigue, and psychomotor agitation or retardation.
• The etiology of depression includes biological factors such as neurotransmitter imbalances (serotonin, norepinephrine, dopamine), genetic predisposition, and neuroendocrine abnormalities.
• Psychosocial factors contributing to depression are chronic stress, trauma, or significant life changes.
• Environmental factors include social isolation, poor support systems, and adverse socioeconomic conditions.

Antidepressants

• Selective Serotonin Reuptake Inhibitors (SSRIs) such as Citalopram, Fluoxetine, Escitalopram, and Sertraline selectively block neuronal reuptake of serotonin, increasing its concentration and activation of postsynaptic receptors.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) such as Desvenlafaxine, Duloxetine, Levomilnacipran, and Venlafaxine block neuronal reuptake of serotonin and NE, with minimal effects on other transmitters.
• Tricyclic Antidepressants (TCAs) such as Amitriptyline, Imipramine, Doxepin, and Clominpramine block neuronal reuptake of norepinephrine and serotonin, increasing their concentrations in CNS synapses.
• Monoamine Oxidase Inhibitors (MAOIs) inhibit the monoamine oxidase enzyme, which breaks down serotonin, norepinephrine, and dopamine.
• Atypical Antidepressants include Bupropion, which inhibits norepinephrine and dopamine reuptake, and Mirtazapine, which antagonizes presynaptic a2 receptors, enhancing norepinephrine and serotonin release, and blocks certain serotonin receptors as well as histamine receptors, promoting sedation and weight gain.

Selective Serotonin Reuptake Inhibitors (SSRIs) Key Points

• SSRIs are contraindicated for patients on MAOIs due to risk of serotonin syndrome.
• Caution should be exercised when using anticoagulants with SSRIs, as both are protein bound.
• SSRIs adverse effects include nausea, headache, sexual dysfunction, insomnia or drowsiness, nervousness, anxiety, mania, sweating, seizures, decreased appetite, and agitation.
• SSRIs drug interactions include avoiding combinations with MAOIs and caution with other serotonergic drugs.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Key Points

• SNRIs may be better tolerated than other antidepressants.
• Precautions for SNRIs include monitoring blood pressure, especially with Venlafaxine, and caution with hypertension.
• Discontinuation symptoms can include anxiety, agitation, tremors, headache, vertigo, nausea, tachycardia, and tinnitus.
• Adverse effects of SNRIs include nausea, headache, anorexia, nervousness, sweating, somnolence, and sexual dysfunction.

Tricyclic Antidepressants (TCAs) Key Points

• TCAs block neuronal reuptake of norepinephrine and serotonin, increasing their concentration.
• Use TCAs with caution in patients with cardiac conduction defects or recent myocardial infarction, and in the elderly; overdose can be life-threatening.
• Adverse effects of TCAs include anticholinergic effects (dry mouth, blurred vision, constipation), cardiovascular effects (orthostatic hypotension, arrhythmias), sedation, weight gain, seizures, and suicidal ideation.
• Drug interactions with TCAs include increased risk of serotonin syndrome when combined with other serotonergic agents and additive CNS depression with alcohol or sedatives.

Monoamine Oxidase Inhibitors (MAOIs) Key Points

• MAOIs inhibit the monoamine oxidase, increasing serotonin, norepinephrine, and dopamine.
• MAOI precautions include food interactions, patients should avoid tyramine-rich foods to prevent a hypertensive crisis.
• Adverse effects include orthostatic hypotension, weight gain, sexual dysfunction, and CNS stimulation.
• Drug interactions include concomitant use with SSRIs, TCAs, sympathomimetics, antihypertensive drugs, and meperidine.

Atypical Antidepressants Key Points

• Bupropion inhibits norepinephrine and dopamine reuptake.
• Bupropion is contraindicated in patients with seizure disorders, or with seizure risk factors.
• Adverse effects of Bupropion include insomnia, agitation, and lowered seizure threshold.
• Drug interactions include drugs that inhibit CYP2B6, MAOIs, other seizure-lowering agents, and alcohol.
• Mirtazapine antagonizes presynaptic a2 receptors and blocks histamine receptors.
• Precautions for Mirtazapine include metabolic and cardiovascular considerations due to sedation and weight gain.
• Trazodone acts as a serotonin receptor antagonist and weak reuptake inhibitor.
• Precautions for Trazodone: contraindicated with concurrent MAOI therapy and known sensitivity to trazodone.
• Adverse effects of Trazodone include sedation, orthostatic hypotension, and rare risk of priapism.

Serotonin Syndrome

• Mental status changes: agitation, confusion, restlessness, anxiety, or excitement.
• Autonomic Hyperactivity: tachycardia, hypertension, hyperthermia, diaphoresis, pupillary dilation.
• Neuromuscular Abnormalities: tremor, clonus, hyperreflexia, muscle rigidity, incoordination.
• Gastrointestinal Symptoms: nausea, vomiting, diarrhea.
• Drugs that elevate Serotonin Syndrome risk: Antidepressants, analgesics, triptans, Linezolid, St. John's Wort, Dextromethorphan and illicit drugs

Suicide Risk with Antidepressant Therapy

• Antidepressants effectiveness should be weighed against the increased risk of suicidal thoughts and behaviors, especially in young individuals.
• Improvement in energy and motivation may occur before mood improves.
• Monitor patients/caregiver should meet with the prescriber at least weekly during the first 4 weeks of treatment, then biweekly for the next 4 weeks, then monthly.
• Watch for symptoms of decline: anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, hypomania, emergence of suicidality.
• Prescriptions should be for the smallest number of doses.

Food-Drug Interactions with MAOIs

• MAOIs with tyramine-rich foods results in a inhibitation of tyramine breakdown, leading to hypertensive crisis.
• Patients on MAOIs should limit aged cheeses, dry/cured meats processed meats, fermented foods, soy products, yeast extracts, and chianti wine.
• Avoid high doses caffeine and excess chocolate(Contains small amounts of tyramine and phenylethylamine).

Drug-Drug Interactions with MAOIs

• Combination of Serotonergic Drugs can lead to serotonin syndrome.
• Use drugs that can intensify the effects of sympathomimetics, lead to dangerous elevations in blood pressure

Bipolar Disorder

• Focus is on treatments to control mood swings, including both manic and depressive episodes.

Mood Stabilizers

• Lithium: regulates neurotransmitter activity.
• Regulated by: valproic acid (Depakene), lamotrigine (Lamictal), and carbamazepine (Tegretol)
• Mechanism: They stabilize mood by reducing abnormal electrical activity in the brain

Antipsychotics

• Treats symptom of mania and sometimes depression
• Include: aripiprazole (Abilify), quetiapine (Seroquel), and olanzapine (Zyprexa)
• Mechanism: They work by altering the effects of neurotransmitters in the brain, particularly dopamine and serotonin

Antidepressants for Bipolar Disorder

• Treat depressive episodes combined with mood stabilizers to prevent triggering mania.
• Selective Serotonin Reuptake Inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline (Zoloft) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) increased levels of serotonin and norepinephrine.

Benzodiazepines

• Short-term treatment to manage anxiety and agitation
• Example: Clonazepam (Klonopin) and lorazepam (Ativan); enhances the effect of the neurotransmitter GABA

Lithium - Key Aspects

• Alters neuronal ion transport and modulates intracellular second messenger systems (e.g., inositol monophosphatase inhibition), affecting neurotransmitter release.
• Requires regular serum level monitoring due to narrow therapeutic index.
• Diuretics (especially thiazides), NSAIDS & ACE Inhibitors increase levels.
• Fine tremor, weight gain, Gl upset.
• Polyuria, polydipsia, hypothyroidism.
• In toxicity: confusion, ataxia, seizures.

Valproic Acid (Valproate) - Key Aspects

• Increases brain GABA levels by inhibiting GABA transaminase.
• Blocks voltage-gated sodium channels, reducing neuronal excitability.
• Monitor liver enzymes and serum ammonia, and check blood counts periodically.
• Increased Lamotrigine levels can be a result of drug interaction

Carbamazepine - Key Aspects

• Blocks voltage-gated sodium channels, stabilizing neurons.
• Reduced drug levels are CYP450 Inducer
• Dizziness, drowsiness, diplopia, ataxia as side affects

Antipsychotics - Key Aspects

• Typical Antipsychotics: Primarily block dopamine D2 receptors.
• Atypical Antipsychotics: Block D2 and 5-HT2A receptors, modulating both dopamine and serotonin signaling.
• Higher risk EPS with typical agents and Metabolic Effects from atypicals

Lithium and Hyponatremia

• Kidneys reabsorb lithium similarly to sodium
• Decreased sodium triggers the kidneys conserve more lithium and lead to lithium toxicity,
• Clients should aim to maintain a stable sodium intake and balanced hydration. -Monitor Diuretic Use and perform Regular Laboratory Monitoring

Lithium Toxicity

• GI: Nausea, vomiting, diarrhea, abdominal pain
• Neuro: Progressing tremors, dizziness, confusion
• Other: Increased thirst/ urination and signs of kidney damage

Antipsychotics - Rational Selection

• Based on symptom profile, side effect risks, comorbidities, and patient-specific considerations.
• First-Generation (FGAS): block dopamine D2 receptors; used for positive symptoms (high EPS risk).
• Second-Generation (SGAS): block D2 and 5-HT2A receptors; used for both positive and negative symptoms.
• AVOID: Metabolic Syndrome, and Dementia in Elderly patients; Monitor for Treatment-Resistant Cases

Key Points for Antipsychotics

• Most FGAs and SGAs are equally effective, except for clozapine.
• SGAs pose a significant risk for metabolic effects, and FGAs cost must less than SGAS -Consider other factors such as symptoms and side affects

Typical Antipsychotics Side Effects

• High risk of EPS, QT prolongation, anticholinergic effects
• Avoid if patient has dementia, heart disease, or sever liver damage

Atypical Antipsychotics Side Effects

• Avoid if patient has metabolic disorder so to weight gain
• May cause hyperprolactinemia (Risperidone, Paliperidone)
• Agranulocytosis risk, so Clozapine is contraindicated in agranulocytosis

Low potency FGAs

• More sedation, anticholinergic effects, and hypotension but less EPS.

High potency FGAs

• More EPS and prolactin elevation, but less sedation & anticholinergic effects.

Medium potency FGAs

• Balanced effects between sedation and EPS risks

Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS)

• Key distinctions between NMS (dopamine D2 receptor blockade) and SS (excess serotonin)
• Neuromuscular hyperactivity (tremors, hyperreflexia, myoclonus, clonus) in SS vs. "Lead pipe" muscle rigidity in NMS.
• Discontinue serotonergic drug or antipsychotic depending on condition and administer other medications.
• High mortality rate for untreated

Extrapyramidal Side Effects (EPS) with Antipsychotics

• Result due to dopamine D2 receptor blockade
• Four components: Acute dystonia, Akathisia, Pseudoparkinsonism, and Tardive Dyskinesia

EPS types components

• Acute Dystonia: spasms (hours to days) give Benztropine to treat
• Akathisia: restless (days to weeks) give Propranolol to treat
• Pseudoparkinsonism: Bradykinesia (movement), shuffling gait (weeks to months) give Benztropine, Trihexyphenidyl to treat
• Tardive Dyskinesia: repetitive movements (months to years) discontinue to treat