Medication History: How to Identify Treatment Resistance and Avoid Repeating Failed Trials
This is Part 7 in our series on Past Psychiatric History.
Read Part 6: Psychotherapy History – How to Assess Engagement and Relational Patterns for the previous component.
Having explored how relational interventions shape healing, we now turn to pharmacologic approaches: biological interventions targeting symptoms directly. Medication history reveals the patient’s unique pharmacological story: what has silenced symptoms, what has failed despite adequate trials, and what side effects have proven intolerable.
A detailed medication history is essential because it avoids repeating failures, builds on successes, identifies tolerability issues, reveals adherence patterns, assesses treatment resistance, and informs realistic expectations. How patients describe medication experiences also reveals cognitive style and engagement patterns that inform your formulation.
Learning Objectives
After reading this section, you should be able to:
- Identify relevant chart sources for previous medication trials
- Gather structured information about each medication trial including dose, duration, response, and tolerability
- Distinguish adequate trials from inadequate trials
- Recognize patterns of treatment resistance and side effect sensitivity
- Document medication history accurately at the level appropriate for each clinical scenario
Start With Chart Review
Before interviewing the patient, review available documentation for medication history:
Past medication lists – Look for psychiatric medications, doses, and dates. Note gaps that may indicate discontinuation periods.
Pharmacy fill records – Reveal actual adherence patterns. Multiple early refills or long gaps between fills provide adherence data the patient may not volunteer.
Prior psychiatric evaluations – Often include detailed medication trials with response and side effect information.
Discharge summaries – Document medication changes during hospitalizations, responses to acute interventions, and discharge regimens.
Laboratory records – Therapeutic drug monitoring (lithium, valproate levels), metabolic monitoring (weight, glucose, lipids), and genetic testing results (pharmacogenomic panels).
Consultation notes – Medical specialists often document psychiatric medication side effects (e.g., cardiology notes about QTc prolongation, endocrinology notes about metabolic effects).
💡 Clinical Pearl: Chart review identifies objective data about adherence, therapeutic doses, and documented side effects before the interview. Pharmacy records showing 90-day supplies picked up every 120 days reveal non-adherence the patient may not report.
Interview the Patient
After chart review, explore medication experiences directly with the patient. This conversation reveals not just what was tried, but how the patient understands their pharmacological journey.
Opening Questions
Start broadly to establish the medication history scope:
- “What psychiatric medications have you tried in the past?”
- “What medications are you currently taking?”
- “Have you ever taken medication for depression, anxiety, sleep, or other mental health concerns?”
For current medications:
- “What dose are you taking?”
- “How long have you been on this dose?”
- “How well is it working?”
- “Any side effects you’ve noticed?”
Information to Gather for Each Medication
For every medication tried, document these essential elements:
Basic Identification
- Medication name (generic and brand – patients often remember brand names)
- Indication (what it was prescribed for)
- Prescriber and treatment setting
Dosing Details
- Starting dose and final dose achieved
- Frequency of administration
- Duration of trial at therapeutic dose
- Whether dose was adequately titrated
Response
- Did it help? Which symptoms improved?
- How much improvement? (Percentage or descriptive scale)
- How quickly did it work?
- How long did benefit last?
Tolerability
- Any side effects experienced?
- Were they tolerable or intolerable?
- Did side effects improve over time?
- Did side effects lead to discontinuation?
Discontinuation
- Why was it stopped? (Lack of efficacy, side effects, practical reasons, feeling better)
- Who made the decision? (Patient, prescriber, collaborative)
- Was discontinuation gradual or abrupt?
- Any withdrawal symptoms?
💡 Clinical Pearl: How a medication was ended matters enormously. Medications stopped because “I felt better” differ from those stopped due to intolerable side effects or lack of response. The former suggests potential for relapse; the latter informs future medication selection.
Critical Concept: Adequate Trials
A medication trial is only meaningful if it was adequate. An adequate trial requires three elements:
Appropriate Dose – Within therapeutic range for the condition being treated. Subtherapeutic doses cannot be considered failed trials.
Sufficient Duration – Long enough for the medication to work:
- Antidepressants: 4 to 8 weeks at therapeutic dose
- Mood stabilizers: 3 to 6 months for full effect
- Antipsychotics: 2 to 4 weeks for acute symptoms, longer for negative symptoms
- Anxiolytics: 2 to 4 weeks for SSRIs/SNRIs; benzodiazepines work immediately
Good Adherence – Actually taking the medication as prescribed. Missing multiple doses weekly means the trial was not adequate.
💡 Clinical Pearl: Many patients report a medication “didn’t work” when they took subtherapeutic doses briefly. A patient who took sertraline 25 mg for 2 weeks has NOT had an adequate trial – they’ve demonstrated intolerance to initiation side effects, which differs from true non-response. Document whether trials were adequate, not just whether medications were tried.
Common Pitfalls in Medication History
🚩 Pitfall: Accepting “I’ve Tried Everything”
A patient reports they’ve “tried everything” and “nothing works.” Detailed questioning reveals multiple trials at subtherapeutic doses for insufficient durations, stopped due to side effects before reaching therapeutic window.
The lesson: This patient hasn’t “tried everything” – they’ve had multiple inadequate trials. Rather than moving to complex augmentation strategies, recommend an adequate trial at therapeutic dose with proper expectation-setting about initial side effects and time to benefit.
Always document:
- Whether trials were adequate
- Specific reasons for inadequacy (dose, duration, adherence)
- Whether the pattern suggests treatment resistance or treatment intolerance
Organizing Medication History by Class
For clarity in documentation and pattern recognition, organize medications by pharmacologic class:
Antidepressants – SSRIs, SNRIs, TCAs, MAOIs, bupropion, mirtazapine, others
Anxiolytics – Benzodiazepine receptor agonists, buspirone, gabapentin, hydroxyzine
Sleep Medications – Benzodiazepine receptor agonists, sedating antidepressants, melatonin, orexin antagonists, quetiapine
Mood Stabilizers – Lithium, valproate, carbamazepine, lamotrigine, oxcarbazepine
Antipsychotics – First-generation (typical) and second-generation (atypical)
Stimulants and ADHD Medications – Methylphenidate, amphetamines, atomoxetine, guanfacine
Side Effect Medicating Medications – Benztropine, Valbenazine, Deutetrabenazine
Substance Use Disorder Medications – Naltrexone, Acamprosate, Disulfiram, Suboxone, Methadone
This organization reveals patterns: “Patient has tried six SSRIs with minimal benefit but responded well to bupropion” suggests different pathophysiology than “Patient responded to multiple SSRIs but could not tolerate side effects.”
Special Considerations
Adherence Patterns
Explore not just what was prescribed but whether it was actually taken:
- “How consistent were you about taking it?”
- “Did you ever miss doses or stop taking it without telling your doctor?”
- “What made it hard to take the medication regularly?”
Patterns of non-adherence inform formulation and future treatment planning. Some patients stop medications when feeling better (lack of illness insight). Others stop due to side effects but don’t report this to prescribers. Some face practical barriers (cost, pharmacy access, complex regimens).
Medication-Induced Adverse Effects
Some patients have experienced serious adverse effects that profoundly shape willingness to try medications:
- Severe akathisia or dystonia
- Serotonin syndrome
- Lithium toxicity
- Neuroleptic malignant syndrome
- Severe weight gain (>20% of body weight)
- Sexual dysfunction leading to relationship problems
- Cognitive impairment affecting work or school
Document these carefully – they represent red lines the patient may not cross again. These experiences appropriately increase caution about future medication trials and require extensive informed consent and monitoring.
Electroconvulsive Therapy (ECT) History
If the patient has received ECT, document:
- When administered (dates of treatment course)
- Number of treatments in the series
- Electrode placement (bilateral, right unilateral, bitemporal)
- Response and duration of improvement
- Side effects experienced (memory impairment, cognitive effects, headache)
- Maintenance ECT (if applicable – frequency and ongoing response)
💡 Clinical Pearl: Patients who responded well to ECT previously are likely to respond again if depression recurs. This history is invaluable for treatment planning in severe, treatment-resistant depression. Prior ECT response is one of the strongest predictors of future ECT response.
Cognitive Style Revealed Through Medication Descriptions
How patients describe medication experiences reveals thinking patterns:
- Rigid, black-and-white thinking: “It didn’t work at all” vs. nuanced reflection “It helped my sleep but not my depression”
- Catastrophizing: “The side effects were unbearable” for mild, transient nausea
- Health anxiety: Detailed recall of every dose change and minor side effect
- Disengagement: Vague responses, inability to recall medication names or doses
- External locus of control: “The doctor kept changing my medications” vs. “We worked together to find the right one”
These patterns inform your understanding of personality structure, health literacy, and capacity for collaborative treatment planning.
What to Document
Your documentation should capture not just what medications were tried, but the quality of each trial and patterns that emerge.
| Documentation Level | What to Include | Example | When to Use This Level |
|---|---|---|---|
| Minimal | Current medications with doses; major past trials with basic outcome | “Patient currently taking sertraline 100 mg daily with good response. Previously tried escitalopram (stopped due to nausea) and fluoxetine (minimal benefit).” | Straightforward medication history; clear current regimen; no concerning patterns; routine follow-up visits |
| Standard | Minimal + Specific doses and durations for past trials; side effects; reasons for discontinuation; adherence patterns | “Patient currently taking sertraline 100 mg daily (started 6 months ago) with 70% improvement in depressive symptoms. Previously tried escitalopram 10 mg for 6 weeks (stopped due to persistent nausea despite antiemetics) and fluoxetine 40 mg for 12 weeks (minimal improvement, adequate trial). Reports consistent adherence with current regimen. No significant side effects on sertraline.” | Multiple medication trials; need to guide future prescribing; some adherence concerns; documenting adequate vs. inadequate trials |
| Detailed | Standard + Assessment of trial adequacy; treatment resistance patterns; detailed side effect profiles; formulation implications; specific recommendations for future trials | “Patient has extensive psychopharmacology history notable for treatment-resistant depression. Has completed adequate trials (>8 weeks at therapeutic dose with good adherence) of five SSRIs (sertraline 200 mg, escitalopram 20 mg, fluoxetine 60 mg, paroxetine 40 mg, citalopram 40 mg) with 20 to 30% improvement only. Partial response to bupropion XL 300 mg (50% improvement) but discontinued due to increased anxiety. Unable to tolerate venlafaxine (severe nausea at 75 mg despite slow titration). Currently on duloxetine 60 mg with modest benefit. Has never tried TCA or MAOI due to prescriber concern about side effects. Patient reports excellent adherence, confirmed by pharmacy records. Side effect profile notable for GI sensitivity (nausea with multiple agents) and prior sexual dysfunction on paroxetine. PHQ-9 scores have ranged from 15 to 22 over past 2 years despite treatment.” | Treatment-resistant presentation; multiple adequate trials; need to justify next-step treatments; complex medication history requiring interpretation; consultation or referral documentation |
Why This Information Matters
A patient’s medication history is far more than a list of drugs tried. It reveals their unique biological response profile, treatment resistance patterns, side effect vulnerabilities, and capacity for adherence. This information is essential for several critical clinical functions:
Avoiding Futile Repetition: Without detailed medication history, clinicians risk repeating failed trials. A patient who has completed adequate trials of five SSRIs is unlikely to respond to a sixth. Understanding this pattern directs treatment toward mechanistically different interventions – MAOIs, TCAs, augmentation strategies, or ECT – rather than cycling through similar medications indefinitely.
Building on Previous Success: Medications that worked before often work again. A patient who responded well to bupropion in the past but stopped it due to life circumstances may respond again. Knowing what has helped provides a pharmacological roadmap when symptoms recur.
Predicting Tolerability: Side effects that caused discontinuation previously will likely recur with rechallenge. A patient who developed severe akathisia on risperidone faces similar risk with other high-potency antipsychotics. This knowledge guides medication selection and monitoring intensity.
Assessing True Treatment Resistance: Multiple failed medication trials do not necessarily indicate treatment-resistant illness. Many apparent “failures” reflect inadequate trials – subtherapeutic doses, insufficient duration, or poor adherence. Distinguishing inadequate trials from true non-response fundamentally changes the treatment approach. True treatment resistance (multiple adequate trials without response) suggests more severe pathophysiology and warrants consideration of advanced interventions like ECT, esketamine, or specialized augmentation strategies.
Understanding Adherence Capacity: Patterns of medication adherence reveal critical information about illness insight, practical barriers, health literacy, and motivation for treatment. A patient who stops medications when feeling better lacks illness awareness. One who can’t afford medications faces practical barriers requiring social work intervention. Another who fears side effects needs extensive psychoeducation and close monitoring. These patterns inform not just what to prescribe, but how to support treatment adherence.
Informing Diagnostic Clarity: Medication response patterns sometimes clarify diagnosis. A patient diagnosed with unipolar depression who became manic on antidepressants may have bipolar disorder. One who responded robustly to stimulants for “depression” may have had unrecognized ADHD. Antipsychotic response at low doses sometimes suggests underlying psychotic process not apparent in initial presentation.
Medication history transforms from a rote checklist into a window on treatment resistance, biological vulnerabilities, and future treatment trajectories. A carefully gathered medication history turns patterns of pharmacologic response into actionable formulation, directly shaping evidence-based prescribing and realistic expectations for patients and families.
Next in this series: Part 8 – Substance Use History: Understanding Self-Medication and Comorbidity
Previous post: Part 6 – Psychotherapy History: How to Assess Engagement and Relational Patterns
