Conditions We Treat · Beachwood, Ohio
Treatment-Resistant Depression
What the term actually means, what is worth ruling out before you accept it, and which options are left when two antidepressants have not worked. Serving Cleveland, Beachwood, and Northeast Ohio.
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Treatment-resistant depression means depression that has not improved enough after at least two different antidepressants, each taken at an adequate dose for an adequate length of time, during the current episode.
It is a description of what has been tried so far. It is not a statement that nothing will work, and it is not something you failed at.
CarePoint Infusion Center in Beachwood provides two treatments for this situation: SPRAVATO® (esketamine) nasal spray and intravenous ketamine therapy. Both require a prescriber. Call (216) 755-4044 with questions.
What "adequate trial" actually means
The definition hinges on a phrase that often goes unexamined. A medication only counts as a failed trial if it was a real trial.
In research and in most insurance policies, that means roughly six to eight weeks at a therapeutic dose. A drug you stopped after ten days because it made you nauseated was not an adequate trial. Neither was one you stayed on for a year but never increased past the starting dose, which is a more common problem than people expect. Neither was one you were prescribed but could not consistently afford or remember to take.
This matters for two practical reasons. Clinically, it changes what your prescriber should do next: the answer to an inadequate trial is usually to run an adequate one, not to escalate to something more invasive. Administratively, it determines whether an insurer will authorize treatments like SPRAVATO, because they will ask for the dose and the duration of each prior medication, not just its name.
How common this is
The largest real-world study of sequential antidepressant treatment, called STAR*D, followed more than 3,600 adults through up to four successive medication steps. Remission rates fell sharply as people moved down the list: about 37 percent reached remission on the first antidepressant, 31 percent of those remaining on the second, and only about 14 percent on the third and again on the fourth.
Two things follow from that pattern. The first is that needing more than one or two medications is ordinary, not unusual. The second is more clinically useful: once two antidepressants from similar families have failed, the odds that a third from the same families will succeed are substantially lower. That declining curve is the main reason specialists start considering treatments that work through a different mechanism rather than continuing down the same list.
Research Reference
Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. The American Journal of Psychiatry. 2006;163(11):1905-17. PubMed: 17074942
What to rule out before accepting the label
Several conditions produce depression that looks resistant but is actually something else, or something treatable that has been missed. It is worth going through this list with your prescriber before concluding that your depression is treatment-resistant, because the answer changes what you should do next.
Worth revisiting with your prescriber
- Dose and duration. The most common cause of apparent resistance. Was each medication pushed to a therapeutic dose, and held there long enough?
- Whether the doses were actually taken. Not a judgment. Cost, side effects, and the memory problems that come with depression itself all interfere, and it changes the interpretation.
- Bipolar disorder diagnosed as unipolar depression. Bipolar illness often first presents as depression, and antidepressants alone can be ineffective or destabilizing in it. A history of periods of unusually elevated mood, reduced need for sleep, or impulsive behavior is worth raising explicitly.
- Obstructive sleep apnea. Fragmented sleep produces fatigue, low mood, and poor concentration that no antidepressant will fix.
- Thyroid disease, anemia, and low vitamin D. All treatable, all commonly missed, all capable of mimicking or worsening depression.
- Chronic pain. Persistent pain and depression maintain each other, and treating only one side tends to disappoint.
- Alcohol and substance use. Alcohol in particular is a depressant and will blunt the effect of any antidepressant.
- Ongoing circumstances. Grief, an abusive relationship, caregiving strain, or financial crisis are not treated by medication, and medication alone will usually underperform while they continue.
None of this means your depression is not real or not severe. It means the label should be earned before it is applied, because it determines what gets tried next.
The options when it is treatment-resistant
Several approaches have evidence behind them. They are not ranked here, because the right one depends on your history, your other medical conditions, your insurance, and what you are willing to do. The table notes which are available at CarePoint and which are not.
| Approach | What it involves | Where |
|---|---|---|
| Optimize or switch | Raising the dose of your current antidepressant, or moving to one from a different class | Your prescriber |
| Augmentation | Adding a second agent such as lithium, thyroid hormone, or an atypical antipsychotic to your current antidepressant | Your prescriber |
| Psychotherapy | Structured approaches such as cognitive behavioral therapy, used alone or alongside medication | A therapist |
| SPRAVATO® (esketamine) | FDA-approved nasal spray for TRD, self-administered under supervision with a required two-hour monitoring period. Covered by many plans with prior authorization | CarePoint |
| IV ketamine | Intravenous infusion, used off-label for depression. Not usually covered by insurance, so typically self-pay, but allows precise dose adjustment during the infusion | CarePoint |
What CarePoint provides
Both of our treatments act on the brain's glutamate system through the NMDA receptor, rather than on serotonin and norepinephrine the way standard antidepressants do. That different mechanism is why they are considered after conventional medications have not worked, and why improvement is often noticed in days rather than weeks.
SPRAVATO® (esketamine) nasal spray
FDA-approved specifically for treatment-resistant depression in adults. You administer the spray yourself in our office under supervision, then stay for a required two-hour monitoring period. Because it is FDA-approved, it is billable to most insurance plans with prior authorization. Since January 2025 it has been approved both on its own and alongside a daily oral antidepressant.
Full details on SPRAVATO treatment, including the schedule, safety information, and the REMS program requirements.
Intravenous ketamine
Ketamine is FDA-approved as an anesthetic; its use for depression is off-label, which is common in psychiatry but means insurance rarely covers it. Delivered by IV, it reaches the bloodstream completely and the rate can be adjusted during the infusion. Read about IV ketamine therapy, or see our comparison of IV ketamine and SPRAVATO.
Research Reference
Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. The American Journal of Psychiatry. 2019;176(6):428-438. PubMed: 31109201
Reif A, Bitter I, Buyze J, et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression. The New England Journal of Medicine. 2023;389(14):1298-1309. PubMed: 37792613
Daly EJ, Trivedi MH, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903. PubMed: 31166571
How to prepare
The single most useful thing you can do before a first appointment is assemble your medication history. Insurers require it, and incomplete history delays more authorizations than anything else.
- List every antidepressant you have tried. For each one, note the approximate dates, the highest dose you reached, how long you stayed on it, and why you stopped — whether it did not help, caused side effects, or stopped working over time. An informal list is far better than nothing while formal records are requested.
- Gather your current medications. Include over-the-counter products, vitamins, supplements, and nasal sprays. Some interact, and nasal corticosteroids and decongestants affect the timing of SPRAVATO dosing.
- Identify your prescriber. We coordinate with the physician or nurse practitioner managing your psychiatric care and send treatment updates to them. If you do not currently have one, tell us when you call.
- Bring recent depression scores if you have them. A PHQ-9 or MADRS score within the last few months supports the authorization. If you do not have one, it can be completed at intake.
- Plan your transportation. You cannot drive yourself home after SPRAVATO or ketamine. Arrange a ride for treatment days before you schedule.
Common questions
What is treatment-resistant depression?
Depression that has not responded adequately to at least two different antidepressants during the current episode, when each was taken at an effective dose for long enough — usually six to eight weeks. It is a practical description rather than a separate diagnosis, and different specialists and insurers apply slightly different criteria.
How many antidepressants do I need to have tried?
Two is the usual threshold, and both have to have been adequate trials. A medication stopped after two weeks for side effects, or never raised past a starting dose, does not usually count. Insurers want the names, doses, durations, and reasons for stopping.
Does this mean nothing will work?
No. It describes what has been tried, not what is possible. In STAR*D, remission fell from about 37% on the first antidepressant to roughly 14% on the third and fourth — which is precisely why specialists shift to a different mechanism rather than trying a fifth similar drug. Several options remain.
What should be ruled out first?
Inadequate dose or duration most often. Also bipolar disorder misdiagnosed as unipolar depression, untreated sleep apnea, thyroid disease, anemia, low vitamin D, chronic pain, alcohol or substance use, and ongoing life circumstances. A careful prescriber revisits these before applying the label.
What treatments are available?
Optimizing or switching your antidepressant, augmenting with lithium, thyroid hormone, or an atypical antipsychotic, psychotherapy, SPRAVATO, IV ketamine, TMS, and ECT. We provide SPRAVATO and IV ketamine. We do not provide TMS or ECT and will tell you if one of those fits your situation better.
Do I need a psychiatrist to be treated here?
You need a prescriber managing your psychiatric care — usually a psychiatrist, sometimes a primary care physician or psychiatric nurse practitioner. We administer treatment and monitor you; we do not replace your prescriber, manage your oral medications, or provide therapy. Call us if you do not currently have a prescriber.
Does SPRAVATO still require an oral antidepressant?
Not necessarily. In January 2025 the FDA approved SPRAVATO as a standalone monotherapy for TRD alongside its existing combination approval, so either is appropriate and the choice belongs to your prescriber. Some insurance policies have not been updated and may still ask for a concurrent oral antidepressant. For the separate indication of depression with acute suicidal ideation, an oral antidepressant is still required.
Will insurance cover it?
SPRAVATO is FDA-approved and covered by many commercial plans, Medicare, and Ohio Medicaid plans, nearly always with prior authorization requiring two documented antidepressant failures and a recent PHQ-9 or MADRS. IV ketamine for depression is off-label and rarely covered, so it is usually self-pay. See what insurance covers.
How quickly do these work?
Oral antidepressants generally take four to six weeks for full effect. Esketamine and ketamine act on the glutamate system and improvement is often noticed within days. Speed is not durability, though — early gains still need an ongoing schedule and continued psychiatric care, and not everyone responds.
What should I bring to a first appointment?
Your antidepressant history with doses, durations, and reasons for stopping; your current medication list including supplements; your prescriber's contact information; your insurance card; and any recent depression questionnaire scores. Incomplete medication history is the most common cause of authorization delays.
Serving Northeast Ohio Communities
CarePoint Infusion Center is in Beachwood just off I-271, roughly 20 minutes from downtown Cleveland. Distance matters more than usual for these treatments: SPRAVATO requires a two-hour monitoring stay twice a week during the first month, and you cannot drive yourself home afterward. A shorter drive makes the schedule realistic.
We conveniently serve patients from:
And throughout Cuyahoga County and Northeast Ohio. Call (216) 755-4044 to ask about treatment in Beachwood.
Getting started
If two antidepressants have not worked and you want to know whether SPRAVATO or IV ketamine makes sense for you, call (216) 755-4044 or send us a message. We will walk through your history, coordinate with your prescriber, and verify your benefits before anything is scheduled.
CarePoint Infusion Center
23215 Commerce Park, Suite 318, Beachwood, OH 44122
Phone (216) 755-4044 · Fax 330-967-0571 · [email protected]
Monday–Thursday 8:00 AM–5:00 PM, Friday 8:00 AM–12:00 PM
If you are in crisis, do not wait for an appointment. Call or text 988, or call 911.
Related pages
- SPRAVATO® (esketamine) nasal spray
- SPRAVATO treatment near Cleveland
- IV ketamine therapy
- IV ketamine compared with SPRAVATO
- What insurance covers
- All conditions we treat
Medical disclaimer. This page is general education, not medical advice, a diagnosis, or a treatment recommendation, and it does not replace care from a qualified mental health professional. Treatment-resistant depression is defined differently by different clinicians, guidelines, and insurance policies; only your prescriber can determine whether the term applies to you and what should be tried next. SPRAVATO carries an FDA boxed warning for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors, and is available only through the SPRAVATO REMS program. Ketamine used for depression is an off-label use. Both are prescription treatments requiring a physician order, and neither is appropriate for everyone. Individual results vary and no outcome is promised. CarePoint Infusion Center does not provide emergency psychiatric services, crisis care, psychotherapy, or inpatient treatment. If you are having thoughts of harming yourself, call or text 988, call 911, or go to the nearest emergency department.