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United States · Clinical guide

Psychiatric care for treatment-resistant depression

When two or more antidepressant trials at an adequate dose and duration have not brought relief, care shifts to a focused re-review and interventional options. This is a turning point in treatment — not a dead end.

How it's treated
A structured re-review, medication optimization or augmentation, TMS, SPRAVATO®, or ECT.
Typical course
Varies by option: TMS typically runs 36 weekday sessions over 6–9 weeks; SPRAVATO® starts twice weekly and tapers over months.
When to seek help
Two or more antidepressants, each tried at an adequate dose for at least 6–8 weeks, without meaningful improvement.
Insurance
Many plans cover TMS and SPRAVATO® for documented treatment resistance, almost always with prior authorization and records of past trials.

The short version

  • There is no single official definition; most clinicians use no meaningful response to two adequate antidepressant trials.
  • Before escalating, good clinics re-check the diagnosis, dosing, adherence, and conditions that can mimic depression.
  • The three interventional options with the strongest evidence are ECT, TMS, and SPRAVATO®.
  • SPRAVATO® is FDA-approved for treatment-resistant depression and dispensed only in REMS-certified settings.
  • Documenting each past medication trial — drug, dose, duration — is what unlocks insurance coverage for the next step.

What treatment-resistant means

There is no single official definition. Most clinicians use the working definition of no meaningful response to two or more antidepressant trials, each at an adequate dose for at least six to eight weeks. By that definition, a substantial share of people with depression pass through it at some point.

Step one: make sure the plan was right

Good clinics re-review before escalating. Common findings that change the picture: an undiagnosed bipolar spectrum condition, untreated ADHD, PTSD, sleep apnea, alcohol or substance use, an inadequate dose or duration, or medications taken inconsistently. Each of these has a different fix — and several of them make standard antidepressant escalation the wrong move.

Documentation matters here: a written list of each past trial — drug, dose, how long — is what insurance companies require before approving the next step.

Interventional options, strongest evidence first

  • ECT remains the most effective acute treatment for severe depression, with response rates other treatments do not reach. It requires anesthesia and can affect memory, which is why it is usually reserved for severe or life-threatening illness.
  • TMS is FDA-cleared for depression that has not responded to medication. It is noninvasive, requires no anesthesia, and typically involves 36 short weekday sessions over six to nine weeks. Side effects are mostly limited to scalp discomfort and occasional headache.
  • SPRAVATO® (esketamine nasal spray) is FDA-approved for treatment-resistant depression — as of the 2025 label update, both alongside an oral antidepressant and as monotherapy. It is dispensed only in REMS-certified settings, with at least two hours of monitoring per session and no driving until the next day after restful sleep. Its label carries boxed warnings for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.

IV ketamine infusion is also used for treatment-resistant depression. It has a real evidence base, but it is off-label, usually self-pay, and protocol quality varies considerably between clinics — a distinction we state plainly rather than blur.

What this costs and how coverage works

TMS and SPRAVATO® are commonly covered for documented treatment resistance, almost always with prior authorization and records of past medication trials. ECT coverage varies more by plan and setting. Ask any clinic for written pricing before starting.

What a course of treatment looks like

  1. 1

    Evaluation and diagnosis

    A psychiatric evaluation reviews your symptoms, history, and medicines, and looks for medical causes that can mimic psychiatric conditions. It may include structured rating scales and collateral history from family.

  2. 2

    Care plan and cost review

    The clinic proposes a plan — medication, therapy, or both — and checks your insurance coverage, including any prior authorization requirements.

  3. 3

    Starting treatment

    Medications begin at a starting dose and are adjusted gradually; therapy sessions are scheduled; interventional options come up when first-line care has not worked.

  4. 4

    Follow-up and adjustments

    Regular check-ins track symptoms with measurement tools, review side effects, and adjust doses — or the plan itself — based on response.

  5. 5

    Ongoing care

    After symptoms improve, maintenance treatment lowers the risk of relapse, often coordinated with your primary care doctor or therapist.

Eligibility

Could a psychiatric evaluation help?

A clinic confirms all of this at your consultation. Use it to see whether a consultation is worth booking.

  • Two or more antidepressants tried at full dose for at least six to eight weeks each.
  • You can document your past medication trials, even approximately.
  • Your diagnosis has been reviewed, including screening for bipolar disorder.
  • You are willing to consider interventional options, not just another medication change.
  • You have support for getting to frequent appointments — TMS and SPRAVATO® both require many visits at first.

Questions people ask

How do I prove I have tried enough medications?

Pharmacy fill records and notes from previous prescribers both work, and clinics routinely help patients assemble them. Approximate dates and doses are better than nothing — the review does not have to be perfect to start.

Is SPRAVATO® the same as IV ketamine?

They are related but different. SPRAVATO® is FDA-approved, dispensed through a REMS program, and often insurance-covered for treatment-resistant depression. IV ketamine is off-label, usually self-pay, and protocols vary between clinics.

Will I need treatment forever?

It depends on the option and your response. Some people maintain gains with ongoing medication; TMS and SPRAVATO® both have defined initial courses with maintenance decisions made afterward, based on how symptoms evolve.

Other conditions we cover

Depression

Persistent low mood, loss of interest, and loss of energy that interfere with daily life. Depression is one of the most common conditions psychiatrists treat, and first-line care works for most people who receive it.

Anxiety

Anxiety disorders — generalized anxiety, panic disorder, and social anxiety — respond well to treatment. First-line care combines SSRI or SNRI medication with cognitive behavioral therapy, and often lasts.

PTSD

After trauma, some people develop intrusive memories, avoidance, and constant vigilance that do not fade on their own. Trauma-focused therapy and specific medications have the strongest evidence for PTSD.

OCD

Obsessions are unwanted intrusive thoughts; compulsions are rituals done to neutralize them. OCD responds to a specific combination: exposure-based therapy and high-dose SSRI medication.

Bipolar disorder

A mood condition with episodes of mania or hypomania — unusually elevated or irritable mood and energy — that typically alternate with depression. Getting the diagnosis right matters, because treatment for bipolar disorder differs fundamentally from treatment for depression alone.

Psychiatric clinics near you

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This guide is general information, not medical advice. Only a prescriber who knows your history can say which treatment is right for you. If you are in crisis, call or text 988.

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