9.4 Common Mood, Anxiety, & Psychotic Disorders
Key Takeaways
- Major depressive disorder treatment phases include acute (6-12 weeks), continuation (4-9 months), and maintenance (1-3 years or lifelong); choose antidepressants based on side-effect profiles and contraindications.
- Generalized anxiety disorder and panic disorder are managed with SSRIs, SNRIs, and CBT; avoid long-term benzodiazepine monotherapy due to dependence risks, reserving them for acute distress.
- Schizophrenia is managed with second-generation antipsychotics as first-line due to lower extrapyramidal symptom risk, but requires monitoring for metabolic syndrome; clozapine is reserved for treatment-resistant cases.
- Bipolar I maintenance requires mood stabilizers like lithium (therapeutic level 0.6-1.2 mEq/L, requires renal/thyroid monitoring) or valproate; antidepressant monotherapy is contraindicated in acute mania.
Common Mood, Anxiety, & Psychotic Disorders
Management of mood, anxiety, and psychotic disorders requires a thorough understanding of diagnostic criteria, medication selection, side-effect profiles, and safety monitoring.
Major Depressive Disorder (MDD) Pharmacotherapy
Major Depressive Disorder is diagnosed by at least five of nine SIGECAPS symptoms (Sleep disturbance, Interest loss, Guilt, Energy loss, Concentration difficulties, Appetite changes, Psychomotor agitation/retardation, Suicidal ideation) lasting at least two weeks.
Treatment is structured into three phases: acute (6 to 12 weeks to achieve remission), continuation (4 to 9 months to prevent relapse, maintaining the same dose), and maintenance (1 to 3 years or lifelong in patients with recurrent or severe episodes). First-line agents include Selective Serotonin Reuptake Inhibitors (SSRIs; e.g., sertraline, escitalopram) due to their favorable safety profile. Common side effects include sexual dysfunction, gastrointestinal distress, and mild weight gain. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs; e.g., venlafaxine, duloxetine) are alternative first-line agents, though venlafaxine can cause dose-dependent hypertension, and duloxetine is highly useful in patients with comorbid neuropathic pain.
Atypical antidepressants are selected based on clinical characteristics:
- Bupropion: A norepinephrine-dopamine reuptake inhibitor. It is associated with no sexual dysfunction or weight gain, making it a popular choice. However, it lowers the seizure threshold and is strictly contraindicated in patients with seizure disorders, bulimia, or anorexia nervosa.
- Mirtazapine: An alpha-2 antagonist that causes prominent sedation and weight gain. This is highly beneficial in elderly patients suffering from insomnia and anorexia.
- Tricyclic Antidepressants (TCAs; e.g., amitriptyline, nortriptyline) & Monoamine Oxidase Inhibitors (MAOIs; e.g., phenelzine): Reserved for refractory cases. TCAs carry a risk of lethal cardiac toxicity in overdose due to sodium channel blockade, leading to QRS widening; sodium bicarbonate is the antidote. MAOIs require a low-tyramine diet to avoid hypertensive crisis and a washout period when transitioning to other antidepressants to prevent serotonin syndrome.
Serotonin syndrome is characterized by the triad of altered mental status, autonomic hyperactivity (tachycardia, hyperthermia, diaphoresis), and neuromuscular excitation (clonus, hyperreflexia). Treatment involves discontinuing all serotonergic agents, supportive care, and administering cyproheptadine (a serotonin antagonist) if supportive measures fail.
Generalized Anxiety Disorder and Panic Disorder
Generalized Anxiety Disorder (GAD) is characterized by excessive, uncontrollable worry about multiple domains for at least six months, associated with physical symptoms like muscle tension, restlessness, and fatigue. First-line therapy includes SSRIs, SNRIs, and cognitive behavioral therapy (CBT). Buspirone (a selective 5-HT1A receptor partial agonist) is a non-addictive adjunctive or alternative medication that requires 2 to 4 weeks to take effect. Benzodiazepines should be avoided for long-term management due to the risks of tolerance, physiological dependence, and cognitive/motor impairment (especially in elderly patients).
Panic Disorder is characterized by recurrent, unexpected panic attacks followed by at least one month of persistent worry about future attacks or maladaptive behavioral changes. Acute panic symptoms are managed with short-acting benzodiazepines (e.g., alprazolam or lorazepam) strictly for immediate relief, while maintenance therapy relies on SSRIs, SNRIs, and CBT.
Schizophrenia and Treatment-Resistant Psychosis
Schizophrenia is diagnosed when a patient exhibits at least two active-phase symptoms (delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms) for at least six months, causing significant social or occupational dysfunction.
Pharmacotherapy is divided into first-generation (typical) and second-generation (atypical) antipsychotics. First-generation agents (e.g., haloperidol, fluphenazine) are potent dopamine D2 antagonists. They carry a high risk of extrapyramidal symptoms (EPS), which include acute dystonia (treated with benztropine or diphenhydramine), akathisia (treated with beta-blockers like propranolol), parkinsonism (treated with benztropine or amantadine), and tardive dyskinesia (treated by switching to a second-generation agent or administering valbenazine).
Second-generation agents (e.g., aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) act as serotonin-dopamine antagonists (blocking 5-HT2A and D2 receptors), unlike typical antipsychotics which primarily target D2 receptors. They have a lower incidence of EPS but carry significant risks for metabolic syndrome (weight gain, dyslipidemia, hyperglycemia), particularly olanzapine and clozapine. Ziprasidone is associated with QTc prolongation. Clozapine is reserved for treatment-resistant schizophrenia (failure of two adequate antipsychotic trials) or severe suicidality. It carries a black box warning for agranulocytosis, necessitating strict monitoring of the absolute neutrophil count (ANC). Other serious side effects of clozapine include myocarditis, severe constipation, and seizures.
Bipolar Disorder Management
Bipolar I disorder is defined by at least one manic episode (severe, persistently elevated, expansive, or irritable mood with grandiosity, decreased need for sleep, pressured speech, racing thoughts, and distractibility). Bipolar II is defined by hypomanic episodes and major depressive episodes.
Acute Mania: Treated with mood stabilizers (lithium, valproic acid) or atypical antipsychotics (olanzapine, risperidone, quetiapine, aripiprazole). Severe mania or agitation requires combination therapy (a mood stabilizer plus an atypical antipsychotic). Antidepressant monotherapy is contraindicated as it can precipitate mania or rapid cycling.
Acute Depression: First-line options include quetiapine, lurasidone, cariprazine, or lamotrigine (which requires slow titration to avoid Stevens-Johnson syndrome).
Maintenance Treatment: Lithium remains a gold standard but has a narrow therapeutic window (0.6 to 1.2 mEq/L). Long-term monitoring must include renal function (risk of chronic kidney disease and nephrogenic diabetes insipidus), thyroid function (risk of drug-induced hypothyroidism), and serum calcium. Lithium toxicity presents with tremor, ataxia, confusion, and vomiting; severe toxicity requires hemodialysis. Valproic acid is an alternative for maintenance, requiring monitoring of liver function tests and platelet counts; it is highly teratogenic (neural tube defects). Lamotrigine is primarily used to prevent depressive relapses and has minimal efficacy in preventing or treating manic episodes. Atypical antipsychotics are also utilized for maintenance therapy.
A 35-year-old woman is diagnosed with major depressive disorder. She is concerned about starting medication because she wants to avoid weight gain and sexual side effects, which she experienced with a prior trial of fluoxetine. She has no other medical conditions and no history of eating disorders or seizures. Which of the following medications is the best option for this patient?
A 24-year-old man with a history of schizophrenia is brought to the clinic for a routine follow-up. He has been taking haloperidol 10 mg daily for the past 6 months. His family reports that he has been extremely restless, constantly pacing the floor, and unable to sit still during meals. On examination, he is noted to be shifting his weight from foot to foot and pacing in the examination room. Which of the following is the most appropriate first-line treatment for this patient's motor symptom?
A 28-year-old man is brought to the emergency department by his family because of a 3-day history of extreme agitation, grandiose delusions, pressured speech, and lack of sleep. On examination, he is hyperactive and states he is a prophet. He has a history of a similar episode 2 years ago that required hospitalization, as well as a history of major depressive episodes. His vital signs are stable. Which of the following is the most appropriate maintenance therapy for this patient?