# Clinical Cases: Psychopharmacology Principles

## Case 1: SSRI Initiation and Management

### Patient Demographics
- **Age:** 34 years old
- **Sex:** Female
- **Occupation:** Middle school teacher

### Chief Complaint
"I've felt sad and anxious for months. I think I finally need medication."

### History of Present Illness
The patient is a 34-year-old woman with a 6-month history of persistent depressed mood, anhedonia, insomnia, poor concentration, and fatigue. She also experiences significant generalized anxiety with excessive worry about work performance, her children's safety, and finances. She has tried therapy for 4 months with partial improvement in coping skills but persistent symptoms. She now wishes to try medication.

This is her first major depressive episode. She has no history of manic or hypomanic symptoms. She denies suicidal ideation. She tried St. John's Wort briefly without benefit.

She is otherwise healthy with no significant medical history. She takes no prescription medications. She is married with two children and is not planning pregnancy. She has no known drug allergies.

### Mental Status Examination

**Appearance:** Well-groomed woman, appears tired

**Behavior:** Cooperative, mild psychomotor slowing

**Speech:** Normal rate, soft volume

**Mood:** "Sad and worried"

**Affect:** Dysphoric, anxious, constricted

**Thought Process:** Linear, ruminative

**Thought Content:** Preoccupation with work performance and family safety; no suicidal ideation

**Insight:** Good

**Judgment:** Good

### Screening Measures
- PHQ-9: 16 (moderately severe depression)
- GAD-7: 14 (moderate anxiety)

### Diagnosis
- Major Depressive Disorder, Single Episode, Moderate
- Generalized Anxiety Disorder

### Medication Selection Discussion

**Why SSRI as First-Line:**
- Efficacy for both depression and anxiety
- Generally well-tolerated
- Safe in overdose
- Once-daily dosing improves adherence

**SSRI Selection:**
- Sertraline selected based on:
  - Good evidence base for both MDD and GAD
  - Favorable drug interaction profile (minimal CYP2D6 inhibition)
  - Generally well-tolerated
  - Once-daily dosing
  - Available generically

### Pharmacokinetic Teaching Points

**Absorption:**
- Oral bioavailability ~45%
- Food minimally affects absorption
- Can be taken with or without food

**Distribution:**
- Highly protein bound (~98%)
- Large volume of distribution
- Crosses blood-brain barrier

**Metabolism:**
- Hepatic via CYP enzymes (primarily CYP2D6, CYP3A4)
- Active metabolite (desmethylsertraline) with minimal clinical activity
- Half-life: 26 hours (allows once-daily dosing)

**Elimination:**
- Primarily fecal excretion of metabolites
- Steady state reached in ~1 week
- No dose adjustment for mild-moderate renal impairment

### Prescribing Plan

**Initial Prescription:**
- Sertraline 25 mg daily for 1 week, then increase to 50 mg daily
- Take in the morning (can be activating)
- Starting low minimizes initial side effects

**Patient Counseling:**

*Timeline:*
- Side effects often occur in first 1-2 weeks, then diminish
- Antidepressant effect: Earliest improvement 2-4 weeks
- Full effect: 6-8 weeks
- Do not stop if no immediate improvement

*Common Side Effects:*
- Nausea (take with food, usually resolves)
- Headache (typically temporary)
- Insomnia or drowsiness (adjust timing of dose)
- Sexual dysfunction (may persist; discuss if occurs)
- Initial anxiety/activation (typically transient)

*Serious Side Effects to Report:*
- Worsening depression or new suicidal thoughts
- Signs of serotonin syndrome (agitation, tremor, fever, sweating)
- Easy bruising/bleeding (SSRI effect on platelets)
- Hyponatremia symptoms (elderly - confusion, weakness)

*Discontinuation:*
- Do not stop abruptly
- Sertraline has moderate discontinuation syndrome risk
- Gradual taper when stopping

### Follow-up Plan

**Week 1 (phone):**
- Assess tolerability
- Check for side effects
- Confirm increase to 50 mg

**Week 4 (in-person):**
- Assess early response (PHQ-9, GAD-7)
- If tolerated but insufficient response, increase to 100 mg
- Target dose range: 50-200 mg

**Week 8-12:**
- Assess for remission
- If partial response, consider increasing dose or augmentation
- If non-response, consider switching agents

---

## Case 2: Antipsychotic Selection and Metabolic Monitoring

### Patient Demographics
- **Age:** 24 years old
- **Sex:** Male
- **Occupation:** College student (on medical leave)

### Chief Complaint
"The voices are telling me people are plotting against me."

### History of Present Illness
The patient is a 24-year-old man with a 6-month history of auditory hallucinations, paranoid delusions, social withdrawal, and declining function. He was recently diagnosed with schizophrenia, first episode. He was started on risperidone 2 mg BID in the hospital but developed significant akathisia and elevated prolactin causing gynecomastia. He is being transitioned to a different antipsychotic.

Baseline metabolic panel prior to any antipsychotic:
- Weight: 165 lbs, BMI 24.5
- Fasting glucose: 92 mg/dL
- HbA1c: 5.4%
- Lipid panel: Total cholesterol 178, LDL 105, HDL 48, TG 125
- Blood pressure: 118/76

Family history significant for type 2 diabetes (father, paternal grandmother) and obesity.

### Antipsychotic Comparison Discussion

**First-Generation vs Second-Generation:**
- First-generation (typical): Higher risk of EPS and tardive dyskinesia, but lower metabolic risk
- Second-generation (atypical): Lower EPS risk, but variable metabolic risk

**Second-Generation Antipsychotics - Metabolic Risk Hierarchy:**
- HIGHEST: Olanzapine, clozapine
- MODERATE: Quetiapine, risperidone
- LOWER: Aripiprazole, ziprasidone, lurasidone

**Agent Selection Considerations:**

Given his:
- EPS/akathisia with risperidone
- Hyperprolactinemia
- Family history of diabetes
- Young age (decades of exposure ahead)

**Aripiprazole selected:**
- Lower EPS risk (D2 partial agonist)
- No prolactin elevation (unlike risperidone)
- Weight-neutral to modest weight gain
- Lower metabolic risk
- May cause akathisia (monitor closely)

### Pharmacodynamic Teaching Points

**Mechanism of Action (Aripiprazole):**
- Dopamine D2 receptor partial agonist
  - Acts as antagonist when dopamine is high (mesolimbic - treats positive symptoms)
  - Acts as functional agonist when dopamine is low (mesocortical - may help negative symptoms)
- Optimal D2 occupancy: 65-80% for efficacy without EPS
- 5-HT2A antagonist (contributes to atypical profile)
- 5-HT1A partial agonist (may reduce anxiety)

**Why Lower EPS:**
- Partial agonism means less complete blockade
- Doesn't "overshoot" into extrapyramidal range
- But can still cause akathisia (most common side effect)

**Why No Prolactin Elevation:**
- Partial agonism maintains some dopaminergic tone in tuberoinfundibular pathway
- Prolactin remains normal (unlike risperidone, which causes marked elevation)

### Prescribing Plan

**Transition:**
- Start aripiprazole 5 mg daily while tapering risperidone over 1 week
- Increase aripiprazole to 10 mg daily after 3-5 days if tolerated
- Target dose: 10-15 mg daily

**Monitoring for Efficacy:**
- Positive symptoms (hallucinations, delusions)
- Negative symptoms (flat affect, avolition)
- BPRS or PANSS if available

**Monitoring for Side Effects:**
- Akathisia (most common) - assess with BARS scale
- Activation, insomnia
- Nausea (transient)
- Headache

### Metabolic Monitoring Protocol

**Required Monitoring Schedule (per ADA/APA Consensus):**

| Parameter | Baseline | 4 weeks | 8 weeks | 12 weeks | Quarterly | Annually |
|-----------|----------|---------|---------|----------|-----------|----------|
| Weight/BMI | X | X | X | X | X | X |
| Waist circumference | X | | | X | | X |
| Blood pressure | X | | | X | | X |
| Fasting glucose | X | | | X | | X |
| Fasting lipids | X | | | X | | X* |
| HbA1c | Consider | | | X | | X |

*Every 5 years if normal

**Weight Management:**
- Counsel about healthy diet and exercise at initiation
- Refer to nutritionist if >7% weight gain
- Consider metformin if significant weight gain
- Consider switching agents if severe metabolic effects

**This Patient's Monitoring Plan:**
- Baseline: Weight 165 lbs, BMI 24.5 (healthy)
- Given family history of diabetes, will check HbA1c at baseline and 12 weeks
- Monthly weight checks for first 3 months
- Fasting glucose and lipids at 12 weeks
- If significant metabolic changes, prioritize lifestyle interventions
- Aripiprazole's favorable metabolic profile chosen specifically given his risk factors

### Follow-up Plan

**Week 1:** Phone check - tolerability, akathisia
**Week 2:** In-person - adjust dose if needed, weight check
**Week 4:** Efficacy assessment, weight check
**Week 12:** Full metabolic panel, efficacy assessment

---

## Case 3: Mood Stabilizer Pharmacology - Lithium

### Patient Demographics
- **Age:** 45 years old
- **Sex:** Male
- **Occupation:** Sales manager

### Chief Complaint
"I think I'm stable now, but I want to make sure I understand my medication."

### History of Present Illness
The patient is a 45-year-old man with a 15-year history of Bipolar I Disorder, currently stable on lithium 900 mg daily (lithium level 0.8 mEq/L). He is here for routine follow-up and medication education. He has had 4 manic episodes and 6 depressive episodes over the years, with his last episode (depression) 18 months ago.

He has been on lithium for 10 years with good response - his manic episodes have been completely prevented, and depressive episodes have been less frequent and less severe. He has tried valproate and lamotrigine in the past with less efficacy.

He is interested in better understanding his medication, particularly why he needs regular blood tests and what symptoms to watch for.

### Current Medications
- Lithium 900 mg at bedtime (level 0.8 mEq/L)
- No other psychiatric medications

### Medical History
- Hypothyroidism (developed on lithium, on levothyroxine)
- Mild chronic kidney disease (eGFR 62, attributed to long-term lithium)

### Teaching Points: Lithium Pharmacology

**Mechanism of Action (Incompletely Understood):**
- Modulates intracellular signaling cascades
- Inhibits glycogen synthase kinase-3 beta (GSK-3β)
- Inhibits inositol monophosphatase
- Neuroprotective effects (increases BDNF, gray matter volume)
- Unique anti-suicidal effect (unrelated to mood stabilization)

**Pharmacokinetics:**

*Absorption:*
- Well absorbed orally
- Peak levels in 1-2 hours (immediate release)
- Extended release: Peak 4-5 hours

*Distribution:*
- Not protein bound
- Distributes in total body water
- Volume of distribution: 0.7-1.0 L/kg

*Metabolism:*
- NOT metabolized
- No hepatic involvement (unique among psych meds)
- Eliminated unchanged by kidneys

*Elimination:*
- Half-life: 18-24 hours
- Steady state: 5-7 days
- 95% renal excretion
- Reabsorbed in proximal tubule (competes with sodium)

**Therapeutic Range:**
- Acute mania: 0.8-1.2 mEq/L
- Maintenance: 0.6-1.0 mEq/L
- Toxicity begins: >1.5 mEq/L
- NARROW THERAPEUTIC INDEX

### Monitoring Requirements

**Lithium Levels:**
- Trough level (12 hours post-dose, before morning dose)
- At initiation: Every 5-7 days until stable
- Stable patient: Every 3-6 months
- After dose change: 5-7 days post-change
- If any symptoms of toxicity
- After illness, dehydration, medication changes

**Renal Function:**
- Baseline BUN, creatinine, eGFR
- Every 6-12 months thereafter
- Lithium can cause interstitial nephritis, reduced GFR over time
- This patient: eGFR 62 - mild CKD, continue monitoring closely

**Thyroid Function:**
- Baseline TSH
- Every 6-12 months
- Lithium inhibits thyroid hormone release
- 25-30% develop hypothyroidism (treat with levothyroxine, can continue lithium)
- This patient: On levothyroxine for lithium-induced hypothyroidism

**Other Monitoring:**
- Calcium (lithium can cause hyperparathyroidism)
- ECG if cardiac history (can affect sinus node)
- Weight (some weight gain common)

### Drug Interactions

**Medications that INCREASE lithium levels (toxicity risk):**
- NSAIDs (ibuprofen, naproxen) - reduce renal clearance
- ACE inhibitors, ARBs - reduce renal clearance
- Thiazide diuretics - reduce sodium, increase lithium reabsorption
- Dehydration/volume depletion - concentrates lithium

**Medications that DECREASE lithium levels:**
- Caffeine (mild)
- Theophylline
- Sodium loading
- Osmotic diuretics

**Patient Instructions:**
- Stay well-hydrated (especially in heat, with exercise)
- Avoid NSAIDs - use acetaminophen instead
- Inform all providers you take lithium before starting new medications
- Maintain consistent sodium intake

### Lithium Toxicity

**Signs of Toxicity (level >1.5 mEq/L):**

*Mild (1.5-2.0 mEq/L):*
- Coarse tremor (vs. fine tremor at therapeutic levels)
- Nausea, vomiting, diarrhea
- Confusion, lethargy

*Moderate (2.0-2.5 mEq/L):*
- Ataxia
- Dysarthria
- Myoclonus
- Increased confusion

*Severe (>2.5 mEq/L):*
- Seizures
- Cardiac arrhythmias
- Coma
- Death

**When to Seek Emergency Care:**
- Severe diarrhea or vomiting (dehydration risk)
- Febrile illness with reduced fluid intake
- Confusion, ataxia, severe tremor
- Starting new medication that interacts
- Any concern for toxicity

**Treatment of Toxicity:**
- Hold lithium
- IV fluids for hydration
- Hemodialysis for severe toxicity

### This Patient's Plan

**Current Status:**
- Stable on lithium 900 mg, level 0.8 mEq/L
- Hypothyroidism managed
- Mild CKD - monitor closely

**Ongoing Monitoring:**
- Lithium level every 3 months (given CKD)
- eGFR every 6 months
- TSH every 6 months
- Annual calcium

**Patient Education Provided:**
- Signs of toxicity
- Drug interactions (especially NSAIDs, ACE inhibitors)
- Importance of hydration
- When to seek emergency care

**Follow-up:** 3 months

---

## Image Attribution

![Psychopharmacology Mechanisms](case_01_image.jpg)

*Image: Diagram showing mechanisms of action of major psychotropic drug classes at the synaptic level, including serotonin reuptake inhibition, dopamine receptor interactions, and GABA modulation. Source: Wikimedia Commons. Used for educational purposes under Creative Commons license.*