Treatment-Resistant Depression Case Study: 46-Year-Old Civil Engineer from Nashik Whose Depression Did Not Lift After Two Antidepressants
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Treatment-Resistant Depression Case Study: Patient Background
This treatment-resistant depression case study follows Vikram (name changed), a composite example that reflects how depression that has not responded to treatment is reassessed and managed at Calida Rehab. The details are illustrative and do not describe any one identifiable person.
Vikram is a 46-year-old civil engineer who manages construction projects in Nashik. He lives with his wife, his two teenage children and his mother. About eighteen months before he came to us, he began to lose interest in his work and in the things he used to enjoy. He slept badly, woke at four in the morning and felt a heavy dread about the day ahead. His family doctor started an antidepressant of the SSRI type. After about ten weeks at a standard dose there was almost no change. A second medicine from a different group (an SNRI) was tried for nearly eight weeks. It helped his sleep a little, but his mood stayed low.
By the time his wife called us, he had stopped going to site visits, handed most of his work to a junior colleague and was spending long hours sitting in his car outside the house. Two weeks earlier he had told her that the family would manage better without him. He also said something that she could not forget: “Nothing works on me.” Frightened, she searched for a place that treats depression that does not respond to the first medicines, and she found Calida Rehab.
Before the case itself, a short note. Treatment-resistant depression is usually described as depression that has not improved enough after at least two adequate trials of antidepressants, meaning the right dose, for long enough, taken as prescribed. It does not mean that a person cannot recover. It means that the plan needs a closer look. To see how it fits with other kinds, read our guides on depression, depression treatment and the types of depression. You may also want to read our depression case study.
Symptoms: How the Depression Showed Up Despite Treatment
Vikram did not look like someone in crisis. He was polite, answered every question and apologised often for taking our time. Behind that, the depression was severe and had been present for a long time. The signs included:
- Persistent low mood: a flat, heavy feeling on nearly every day for over a year, with no lift even when good news arrived.
- Early morning waking: he woke at four, could not return to sleep and felt worst in the first half of the day.
- Loss of interest: he had stopped following cricket, stopped his evening walks and no longer joined family meals.
- Slowing down: his speech and movements were slower, and simple tasks took far longer than before.
- Weight and appetite loss: he had lost about six kilograms in four months without trying.
- Guilt and worthlessness: he believed he had failed as a father and as an engineer, and that he was a burden.
- Poor concentration: he missed errors in site reports for the first time in his career.
- Hopelessness about treatment itself: he had decided that no medicine would ever help him.
He also had passive thoughts of death on most days, and had said aloud that his family would manage better without him. He had no plan and no intent to act, but our team treated this as a serious sign, and it shaped the whole plan.
Why Treatment-Resistant Does Not Mean Untreatable
When two medicines have failed, many people and families conclude that nothing will work. That belief can be as harmful as the illness. A few points are worth knowing.
- Many cases of “resistance” are not resistance yet. The dose may have been too low, the trial too short, doses missed, or the medicine stopped early because of side effects. Doctors call this apparent or pseudo-resistance, and it is checked first.
- Other conditions can block recovery. An underactive thyroid, sleep apnoea, alcohol or sleeping tablets, anxiety, chronic pain and unrecognised bipolar disorder can all make depression harder to treat.
- There are many next steps. These include changing the dose, switching to a different medicine, adding a second medicine, structured psychotherapy and brain stimulation treatments such as ECT and rTMS.
- Hopelessness is a symptom. The thought that “nothing will ever work” is often part of the depression, and it usually eases as the depression is treated.
- Many people do improve with later steps. In a large American study of depression treatment (STAR*D), only about a third of people reached full remission with their first antidepressant, and many others improved when the plan was changed.
For Vikram, the turning point was hearing that two unsuccessful medicines were information for the next plan, not a verdict on him.
Diagnosis: How Treatment-Resistant Depression Was Assessed at Calida Rehab
There is no blood test for depression, and no scan that shows treatment resistance. A psychiatrist makes the assessment from a detailed history, a mental state examination and standard rating scales. For Vikram, the assessment included:
- A treatment history, medicine by medicine: the name, dose, start and stop dates and missed doses of each medicine, to judge whether each trial was adequate. His first two trials were adequate in dose and length, and he had taken them regularly.
- Symptom review against DSM-5-TR and ICD-11: a major depressive episode of severe degree, lasting about eighteen months, with no psychotic symptoms.
- PHQ-9 depression scale: his score was 21, in the severe range.
- Suicide risk review: a direct and careful conversation about his thoughts, his reasons for living and his family’s ability to support him. He had passive thoughts, no plan and no intent.
- Screening for bipolar disorder: past periods of high energy, reduced need for sleep or unusual behaviour, and family history. He had none of these. This matters, because some antidepressants can worsen unrecognised bipolar disorder.
- Physical checks: blood tests for thyroid function, blood count, vitamin B12, vitamin D, blood sugar, and liver and kidney function, and an ECG before further medicine changes. His thyroid level was slightly high and was repeated and followed up with a physician.
- Sleep and breathing: because he snored and woke unrefreshed, he was screened for sleep apnoea and referred for a sleep study, which showed moderate sleep apnoea.
- Alcohol use: he had been having two to three drinks most evenings to help him sleep, which he had not mentioned to his earlier doctors.
The diagnosis was major depressive disorder, severe, without psychotic symptoms, that had not responded to two adequate antidepressant trials. Three things were likely to be making it harder to treat: evening alcohol, untreated sleep apnoea and a borderline thyroid result.
Treatment Plan for Treatment-Resistant Depression
No single treatment suits everyone. At Calida Rehab the plan is built after the assessment and reviewed often. For depression that has not responded, the plan looks at the whole picture and not only at the medicine. Vikram’s plan had these parts.
- A supervised stay: because of his hopelessness and passive thoughts of death, the team advised a stay of about three weeks, so that medicine could be changed safely and he could be observed closely.
- Stopping alcohol: alcohol worsens mood and sleep and weakens the effect of antidepressants. His intake was low enough that he did not need a medical detox, but he was monitored, and he agreed to stay alcohol-free.
- A medicine review: the psychiatrist moved him to a third antidepressant with a different way of working, with a gradual and supervised change from the second. He was told that most antidepressants take several weeks to show their full effect, and that he should not stop any medicine on his own.
- Augmentation: after about six weeks at a suitable dose, his PHQ-9 had fallen from 21 to 15, which was progress but not enough. The psychiatrist discussed adding a second medicine to boost the first, explained the options and their side effects, and arranged the blood tests and monitoring that the chosen medicine needed.
- Treating what was in the way: his sleep apnoea was treated through a physician, and his thyroid result was followed up.
- Structured psychotherapy: regular sessions of cognitive behavioural therapy and behavioural activation, starting once his concentration allowed.
- Next-step options explained: the team explained that if medicine and therapy were still not enough, options such as electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS) could be considered, and what each involves. These were not needed in his case.
- Family sessions: his wife and his elder child learned about the illness, the warning signs and how to talk to him without pushing or blaming.
The team also made clear that treatment for depression that has been present for a long time is measured in months, and that every change was made with his agreement.
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Therapies Used in This Treatment-Resistant Depression Case Study
The therapies below were part of Vikram’s plan and are commonly used alongside medicine in depression that has been hard to treat.
- Cognitive Behavioral Therapy (CBT): worked on thoughts such as “nothing works on me” and “my family is better off without me”, and tested them against real events. See our CBT page.
- Behavioral therapy (behavioural activation): planned small, meaningful activities, starting with a ten-minute walk, to rebuild the link between action and mood. See our behavioral therapy page.
- Interpersonal Therapy (IPT): focused on the withdrawal from family and the change in his role at work and at home. See our interpersonal therapy page.
- Family therapy: helped his wife and children understand that his silence was part of the illness and not a lack of love. See our family therapy page.
- Psychoeducation: clear teaching about treatment-resistant depression, how medicines are changed in steps and what to expect at each step. See our psychoeducation page.
- Meditation therapy: a short daily practice that helped him notice low mood and worry without being pulled further into it. See our meditation therapy page.
- Electroconvulsive Therapy (ECT): explained to the family as a later option if the plan had not worked, which is why it is described here. It was not used for Vikram. See our ECT page.
Follow-Up Care After Discharge
For depression that has already lasted more than a year, the plan does not end at discharge. Vikram’s aftercare was written down before he left:
- Weekly therapy for the first two months, then every two weeks.
- Psychiatrist reviews at two weeks, four weeks and eight weeks, then monthly, to check response, side effects, sleep and any blood tests that his medicines need.
- PHQ-9 repeated at each review, so that progress was measured and not guessed.
- Continued medicine for many months after he felt well, with any change decided together with his psychiatrist and never stopped suddenly.
- Continued treatment of sleep apnoea, and no alcohol.
- A short written list of his early warning signs (waking at four, skipping site visits, withdrawing from meals) and who to call.
- A contact number for his wife, with the message that it was fine to call if she saw him slipping.
Depression that has needed several steps to treat tends to need longer follow-up. The length of treatment is decided by the psychiatrist, based on how he responds.
Outcome: What Recovery Looks Like After a Reviewed Plan
What changed for Vikram over the first six months:
- Mood: his PHQ-9 score fell from 21 to 15 at week six, to 11 at week ten, to 8 at month three and to 5 at month six.
- Thoughts: the passive thoughts of death stopped within the first month, and he stopped saying that nothing works on him.
- Sleep: after he stopped alcohol and began treatment for sleep apnoea, he slept through to about six in the morning most nights.
- Work: he returned to office work at month three, in a planned and gradual way, and went back to site visits in month four.
- Family: he attended his son’s cricket match for the first time in over a year, and his wife said she could talk to him again without being afraid.
- Medicine: he took all medicines as advised and kept every review, including in the weeks when he felt well.
It is worth being clear about what recovery means. Not everyone responds at the same step, and some people need more steps than Vikram did. Recovery does not mean that every day is good. It means that depression no longer runs the day, a bad week is recognised early, and the person knows what to do about it.
What the first six months of treatment usually look like
- Weeks 1 to 3: assessment, physical checks, a safe change of medicine and the first therapy sessions, with a supervised stay where needed.
- Months 1 and 2: medicine reviewed and, if the response is partial, a second medicine added; weekly therapy; sleep and activity routines built up.
- Months 3 and 4: a planned return to work and family routines, fortnightly therapy and early warning plan practised.
- Months 5 and 6: monthly reviews if steady, medicine continued, and a plan for the next year.
This is a general guide. Every person moves at a different pace, and the length of stay and follow-up is decided by the treating team.
Key Takeaways from This Treatment-Resistant Depression Case Study
- Treatment-resistant depression is usually defined as depression that has not improved enough after at least two adequate antidepressant trials. It does not mean the person cannot recover.
- The first step is to check that each earlier trial was adequate in dose, length and regular use.
- Alcohol, sleep apnoea, thyroid problems, anxiety and unrecognised bipolar disorder can all make depression harder to treat, and they need to be looked for.
- Next steps include changing or adding medicines, structured psychotherapy and, for some people, ECT or rTMS under specialist care.
- Hopelessness such as “nothing will ever work” is a symptom of depression, and it often eases with treatment.
- Medicines should never be stopped suddenly, and follow-up over many months protects recovery.
When Should You See a Doctor?
Please speak to a doctor or psychiatrist if you or someone you know:
- Has felt low, empty or hopeless for more than two weeks despite taking an antidepressant as advised for six to eight weeks
- Has tried two or more antidepressants without enough relief
- Has stopped medicine because of side effects or because of the belief that nothing will work
- Has thoughts of death, or has said that the family would be better off without them
- Is using alcohol or sleeping tablets to cope with low mood or poor sleep
- Snores loudly, wakes unrefreshed or feels exhausted despite long sleep
- Feels unusually energetic, needs little sleep or becomes irritable after starting a medicine
Please do not stop or change an antidepressant on your own. If someone talks about ending their life, has made a plan or cannot stay safe, do not wait. Call 112 or Tele-MANAS on 14416 and stay with the person until help arrives. You can also call our 24-hour helpline for a confidential conversation. To check how you have been feeling, read our guide on when to take a depression test.
Treatment-Resistant Depression Case Study: Frequently Asked Questions
What is treatment-resistant depression?
Treatment-resistant depression is depression that has not improved enough after at least two adequate trials of antidepressants. Adequate means the right dose, for long enough, taken as prescribed. It is a description of how the illness has responded so far, not a statement that the person cannot get better.
How many medicines must fail before depression is called treatment-resistant?
Most definitions require two antidepressants from different groups, each given at a suitable dose for about six to eight weeks, with the person taking them regularly. Some doctors also use the term difficult-to-treat depression, which looks at all the factors that make recovery harder, and not only the number of medicines tried.
Does treatment-resistant depression mean I will never recover?
No. Many people improve when the plan changes, for example with a different medicine, an added medicine, structured therapy or brain stimulation treatment. The belief that nothing will ever work is itself a common symptom of depression.
Why might antidepressants not work for me?
There are several possible reasons. The dose may have been too low or the trial too short, a dose may have been missed, or the medicine may have been stopped early because of side effects. Other conditions such as thyroid problems, sleep apnoea, alcohol use, anxiety, chronic pain or unrecognised bipolar disorder can also reduce the response.
What is pseudo-resistance?
Pseudo-resistance, or apparent resistance, means that depression looks resistant but earlier treatment was not really adequate, for example because of low dose, short duration or irregular use. Checking for it is the first step in a reassessment, and a properly delivered trial may work.
What are the next steps after two antidepressants fail?
Your psychiatrist will usually review the diagnosis, check for medical and lifestyle factors, and then consider optimising the dose, switching to a medicine with a different action, adding a second medicine, or adding structured psychotherapy. Brain stimulation treatments such as ECT or rTMS may be considered for some people.
Is ECT used for treatment-resistant depression?
ECT is one option for severe depression, including depression that has not responded to medicines. It is given under general anaesthesia and a muscle relaxant, in a hospital setting, after a full assessment and with the person’s consent. Temporary memory problems are a known side effect, and your psychiatrist will explain the benefits and risks before you decide.
Can other conditions make depression harder to treat?
Yes. Thyroid disease, sleep apnoea, alcohol or substance use, anxiety disorders, chronic pain and bipolar disorder can all affect how depression responds. This is why a full assessment, including blood tests and a sleep and substance history, is part of the work-up.
How long should treatment continue after I feel better?
Treatment usually continues for at least six to twelve months after recovery, and often longer when depression has been severe, long-lasting or has returned before. Your psychiatrist decides the length of treatment. Do not stop medicine suddenly or on your own.
Is my information kept private?
Yes. Assessment and treatment details are confidential and are shared with family or employers only with your consent.
Sources and Further Reading
This page is for information and is not a substitute for medical advice. The case described is a composite example, and details are illustrative. If you think you or someone you know may have depression that is not improving, please see a doctor or psychiatrist for a full assessment. If anyone is at risk of self-harm, call 112 or Tele-MANAS on 14416 at once.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). 2022.
- World Health Organization. International Classification of Diseases, 11th Revision (ICD-11), 6A70 Single episode depressive disorder.
- 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. American Journal of Psychiatry, 2006; 163(11): 1905-1917.
- McAllister-Williams RH, Arango C, Blier P, et al. The identification, assessment and management of difficult-to-treat depression: an international consensus statement. Journal of Affective Disorders, 2020; 267: 264-282.
- UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. The Lancet, 2003; 361(9360): 799-808.
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. Journal of General Internal Medicine, 2001; 16(9): 606-613.
- National Institute for Health and Care Excellence. Depression in adults: treatment and management (NG222). 2022.