Subclinical hypothyroidism, T3 augmentation, the underrecognized contributor to TRD.
The seasoned approach
Thyroid evaluation and intervention in psychiatric practice. The discipline that goes beyond ordering TSH — the workup that finds the contributor, the T3 augmentation that is evidence-based and underused, the longitudinal management.
Layer 1— Baseline workup in TRD
TSH, free T4, free T3, thyroid antibodies (anti-TPO, anti-thyroglobulin). The expanded panel is part of TRD workup, not just TSH. Subclinical hypothyroidism (TSH 4.0-10.0 with normal free T4) is associated with depression; low free T3 with normal TSH (low T3 syndrome) is common in TRD; thyroid antibodies suggest Hashimoto's even when TSH is borderline.
Layer 2— Treat subclinical hypothyroidism in depression context
Subclinical hypothyroidism with TSH 4.5-10.0 in patient with depression frequently warrants levothyroxine treatment (despite varying guidelines for asymptomatic patients). Start levothyroxine 25-50mcg, titrate to TSH target of 1.0-2.5. Reassess depression after 8-12 weeks of euthyroid state.
Layer 3— T3 augmentation in TRD
Liothyronine 25-50mcg daily added to antidepressant. Strong evidence base from STAR*D and earlier trials. Particularly effective when subclinical hypothyroidism or low T3 is present, but works in many euthyroid TRD patients. Monitor TSH; usually well-tolerated. The augmentation strategy with substantial evidence that is frequently skipped.
Layer 4— Hashimoto's thyroiditis with neuropsychiatric symptoms
Hashimoto's encephalopathy (rare) presents with cognitive, psychiatric, and neurological symptoms; responds to steroids. More commonly, Hashimoto's produces mood and cognitive symptoms that improve with thyroid optimization. The presence of antibodies changes the treatment threshold.
Layer 5— Hyperthyroidism contributing to psychiatric symptoms
Anxiety, agitation, insomnia, mood lability may reflect underlying hyperthyroidism. The workup identifies the cause; treatment of the hyperthyroidism typically resolves the psychiatric symptoms. Beta-blockers may bridge symptom management. Coordinate with endocrinology.
Layer 6— Long-term thyroid management in psychiatric patients
Lithium can produce hypothyroidism over time — annual TSH monitoring on lithium. Many psychotropics interact with thyroid; medications may need adjustment when thyroid changes. Coordinate with primary care or endocrinology for thyroid management; maintain communication.
Special situations
TRD with low T3 but normal TSH and T4: T3 augmentation reasonable trial; many of these patients respond. Consider hs-CRP given low T3 syndrome correlates with inflammation; broader anti-inflammatory work may help.
Pregnancy and thyroid: Maternal thyroid function affects fetal development; trimester-specific TSH targets. Coordinate with obstetrics; if treating maternal thyroid, monitor carefully through pregnancy.
Patient on lithium for years with rising TSH: Lithium-induced hypothyroidism is common (10-20% of long-term lithium patients). Treat with levothyroxine; do not discontinue lithium for this reason in most cases. Coordinate care.
Patient requesting natural-thyroid preparations (Armour, NP Thyroid): These contain both T4 and T3 in fixed ratios; some patients prefer them. Evidence base is comparable to levothyroxine plus liothyronine combination. Reasonable option if patient preference and tolerability support; coordinate with prescriber. Dose conversion is not straightforward; specialty involvement recommended for the transition.
Generally avoid
TSH alone as adequate thyroid workup in TRD — the expanded panel finds contributors the standard workup misses.
Dismissing TSH 4.5-10 as "normal" in depressed patients — subclinical hypothyroidism in depression frequently warrants treatment trial.
T3 augmentation neglect — STAR*D-quality evidence supports T3 augmentation; many TRD patients have never had a trial.
Ignoring thyroid antibodies in patients with normal TSH — Hashimoto's with normal TSH still affects mood and cognition in some patients.
The chief-resident note: Thyroid workup and intervention in TRD is one of the most underused evidence-based strategies. The patient with treatment-resistant depression and even mild thyroid abnormality may experience substantial improvement with thyroid optimization or T3 augmentation. Build the practice for the expanded workup, the T3 augmentation trial, and the coordinated thyroid management. The work is high-leverage.
Warm cream-tinted manuscript page, deep slate margin annotations, amber palette. Thyroid in mood and cognition — subclinical hypothyroidism, T3 augmentation, the underrecognized contributor to TRD. Margin clusters on the workup beyond TSH and the clinical use of T3.
Thyroid dysfunction and the broader HPT axis are critical to psychiatric assessment, particularly in treatment-resistant depression. The standard TSH-only workup misses meaningful contributors; the expanded thyroid panel (free T4, free T3, antibodies, reverse T3 in selected cases) frequently identifies treatable factors that resolve treatment resistance. T3 augmentation in TRD has strong evidence base going back decades and is frequently underused. The clinical discipline includes the workup, the intervention thresholds, and the coordinated long-term management.
Subclinical hypothyroidism and depression. TSH 4.0-10.0 with normal free T4 — labeled "subclinical" — is associated with depression in epidemiological studies and frequently improves with levothyroxine treatment in patients with depression. The general endocrinology guidance varies on treating asymptomatic subclinical hypothyroidism; the psychiatric context shifts the calculation toward treatment when the patient has depression with inadequate response to standard treatment. Start levothyroxine 25-50mcg; titrate to TSH 1.0-2.5. Reassess depression after 8-12 weeks of euthyroid state.
Low T3 syndrome and treatment resistance. Low free T3 with normal TSH and free T4 is common in TRD populations and has been associated with inflammation, chronic illness, and treatment-resistant depression. The pattern may not appear on standard TSH-only workup. T3 augmentation in these patients is particularly likely to produce response. Liothyronine 25-50mcg daily added to antidepressant; monitor TSH; usually well-tolerated. Response over 4-8 weeks.
T3 augmentation evidence and underuse. The STAR*D trial confirmed T3 augmentation as an effective second-step strategy in TRD, with response and remission rates competitive with other augmentation strategies. Despite this evidence, T3 augmentation remains underused — many TRD patients have never had a trial. The clinical discipline is to consider T3 augmentation as part of standard TRD pathway, particularly in patients with thyroid markers consistent with low T3 or subclinical dysfunction.
Hashimoto's thyroiditis and Hashimoto's encephalopathy. Hashimoto's thyroiditis (autoimmune thyroid disease with anti-TPO and anti-thyroglobulin antibodies) is common and may produce mood and cognitive symptoms even when TSH is normal or borderline. Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis, SREAT) is rare but presents with cognitive, psychiatric, and neurological symptoms — recognition matters because it responds to steroid treatment. The clinical workup includes thyroid antibodies in psychiatric patients with mood and cognitive symptoms.
The longitudinal thyroid management. Patients on lithium require annual TSH monitoring; lithium-induced hypothyroidism is common with long-term treatment and is generally treatable with levothyroxine without discontinuing lithium. Many psychiatric medications interact with thyroid hormones or function. The coordinated care between psychiatry and primary care or endocrinology matters across the years of treatment. The discipline is to engage thyroid evaluation thoroughly in TRD, treat subclinical and low-T3 findings when the depression context warrants, deploy T3 augmentation as the evidence-based strategy it is, and maintain longitudinal monitoring across the long course of treatment.
Editorial illustration of the thyroid workup that goes beyond TSH — free T4, free T3, antibodies, reverse T3, the picture that reveals what TSH alone misses. The discipline of thoughtful thyroid evaluation in psychiatric practice.
The anchor
Thyroid workup in TRD goes beyond TSH (free T4, free T3, antibodies). Subclinical hypothyroidism in depression frequently warrants treatment. T3 augmentation has STAR*D evidence and is underused. Hashimoto's may produce symptoms with normal TSH. Coordinate with primary care/endocrinology.
Painterly editorial illustration of T3 augmentation — the STAR*D evidence, the candidate selection, the dosing, the monitoring. The evidence-based augmentation that is frequently underused.
Prove it
A 51-year-old man with TRD, failed three SSRIs and two augmentation strategies (lithium, aripiprazole). Current TSH 3.8, free T4 normal, free T3 low-normal (2.7 pg/mL, ref 2.3-4.2), thyroid antibodies not previously checked. How do you incorporate thyroid management?