How do you treat biological psychiatric symptoms versus non-biological ones?

Treatment of Biological vs. Non-Biological Psychiatric Symptoms

For biological psychiatric symptoms (e.g., major depression, schizophrenia), initiate treatment with second-generation antipsychotics or antidepressants as first-line pharmacotherapy, while for non-biological symptoms (secondary to medical conditions or psychosocial stressors), address the underlying cause first before considering psychotropic medications.

Distinguishing Biological from Non-Biological Symptoms

Biological Psychiatric Symptoms

• Primary psychiatric disorders include major depressive disorder, schizophrenia spectrum disorders, and bipolar disorder where symptoms arise from neurobiological dysfunction rather than external medical causes 1.
• These conditions require pharmacological intervention as first-line treatment alongside evidence-based psychotherapy 1.
• The American College of Physicians recommends either cognitive behavioral therapy (CBT) or second-generation antidepressants (SSRIs/SNRIs) for major depressive disorder, with moderate-quality evidence showing equivalent efficacy 1.

Non-Biological (Secondary) Psychiatric Symptoms

• Secondary symptoms result from underlying medical conditions (e.g., thyroid disorders, adrenal insufficiency, systemic lupus erythematosus) or medication side effects 2.
• Treatment of the underlying medical condition often results in resolution of psychiatric symptoms without requiring psychotropic medications 2.
• In schizophrenia, secondary negative symptoms can arise from antipsychotic side effects, untreated positive symptoms, or environmental deprivation—these require optimization of the primary treatment rather than additional medications 1.

Treatment Algorithm for Biological Symptoms

Major Depressive Disorder

First-Line Treatment:

• Start with sertraline 50 mg daily or escitalopram 10 mg daily as preferred SSRIs, or offer CBT as monotherapy based on patient preference 3, 4.
• Alternative: Bupropion if sexual dysfunction is a concern, as it has significantly lower rates of sexual adverse events 3.
• Avoid paroxetine due to higher sexual dysfunction rates 3.

Second-Line Treatment (Treatment-Resistant Depression):

• After inadequate response to first SSRI trial (<50% symptom reduction after 6-12 weeks), switch to bupropion, sertraline, or venlafaxine—moderate-quality evidence shows no significant difference between switching options 3, 5.
• Alternatively, augment current SSRI with bupropion, which decreases depression severity more than buspirone augmentation 3.

Third-Line Treatment:

• For patients failing two adequate antidepressant trials, initiate esketamine nasal spray (Spravato) in conjunction with an oral antidepressant 3.

Schizophrenia Spectrum Disorders

Antipsychotic Management:

• Second-generation antipsychotics are first-line treatment for schizophrenia, with consideration for switching from first-generation agents to reduce secondary negative symptoms 6, 7.
• Antipsychotic studies show patients with more severe baseline symptoms (PANSS total >80) require earlier intervention, typically with illness duration <5 years 1.

Negative Symptoms:

• Distinguish primary negative symptoms (intrinsic to illness) from secondary negative symptoms (due to medication side effects, positive symptoms, or environmental factors) 1, 7.
• For secondary negative symptoms: optimize antipsychotic dosing to minimize extrapyramidal side effects and ensure adequate treatment of positive symptoms 7.
• For primary negative symptoms: consider antidepressant add-on therapy, social skills training, or cognitive remediation for patients with cognitive impairment 7.

Treatment Algorithm for Non-Biological Symptoms

Medical Condition-Related Symptoms

Step 1: Identify and Treat Underlying Condition

• Conduct targeted evaluation for medical causes: thyroid function tests, cortisol levels, autoimmune markers (ANA, anti-dsDNA for SLE), neuroimaging if indicated 2.
• In conditions like adrenal insufficiency, appropriate treatment of the underlying condition results in resolution of psychiatric symptoms without psychotropic intervention 2.

Step 2: Monitor Response

• Some conditions (e.g., SLE) may require treatment of both the medical condition and psychiatric symptoms, as treatment of the underlying condition may alleviate but can also exacerbate psychiatric manifestations 2.
• Use collaborative care model involving primary care, mental health, and specialty providers 2.

Medication-Induced Symptoms

• Review all current medications for psychiatric side effects (e.g., corticosteroids causing mood symptoms, beta-blockers causing depression) 8.
• Discontinue or substitute offending agents before initiating psychotropic medications 2.

Psychosocial Interventions Across Both Categories

Evidence-Based Psychotherapy

• CBT monotherapy shows equivalent efficacy to second-generation antidepressants for major depression, with moderate-quality evidence (response RR 0.90, remission RR 0.98) 8, 3.
• CBT has fewer adverse effects and lower relapse rates compared to antidepressants alone in long-term follow-up 8, 3.
• For schizophrenia negative symptoms, social skills training and cognitive remediation are recommended alongside pharmacotherapy 7.

Combination Therapy Considerations

• Low-quality evidence shows no significant difference in response or remission between antidepressant monotherapy and combination therapy with antidepressants plus CBT 1.
• However, one trial showed improved work functioning with combination therapy 1.
• In schizophrenia, 80-90% of patients receiving non-pharmacological interventions are already prescribed antipsychotics, suggesting combination approaches are standard practice 1.

Critical Pitfalls to Avoid

Misattribution of Symptoms

• Never assume psychiatric symptoms are primary without ruling out medical causes—thyroid disorders, autoimmune conditions, and medication effects can mimic psychiatric illness 2.
• In schizophrenia, do not add medications for negative symptoms without first optimizing antipsychotic dosing and ruling out secondary causes (extrapyramidal symptoms, inadequate positive symptom control) 7.

Inappropriate Medication Selection

• Never use beta-blockers (propranolol, atenolol) for major depressive disorder—they lack efficacy evidence and are explicitly deprecated by guidelines 8.
• Avoid paroxetine as first-line SSRI due to higher sexual dysfunction rates 3.

Premature Treatment Escalation

• Allow 6-12 weeks at therapeutic dose before declaring treatment failure and switching or augmenting 3, 5.
• For discontinuation, taper gradually rather than abrupt cessation to minimize withdrawal symptoms (dysphoria, irritability, sensory disturbances) 9.

Monitoring Requirements

• Monitor for suicidality during initial weeks of antidepressant treatment and with dose changes, as risk may increase before therapeutic benefit 5, 9.
• Screen for bipolar disorder before initiating antidepressants, as treating a depressive episode with antidepressants alone may precipitate mania 5.
• Monitor blood pressure with venlafaxine, as sustained hypertension occurs in dose-dependent fashion (13% at >300 mg/day) 5.