COMMENTARY

Treatment-Resistant Depression: The PatientPerspective

Introduction

Depression affects nearly 20 million people in the UnitedStates each year (National Institute of Mental Health2001). Ten to thirty percent of those treated do not respondto antidepressant therapy, and of those who do, 50–75%experience only partial improvement in symptoms (Joeffeet al 1996) or a recurrence of depression while still takingmedication (Fava et al 1995). So, in addition to the pain ofdepression, people with this illness often must deal with thefrustration of treatment resistance. Many have inadequatesupport systems and incomplete or incorrect information, sotreatment resistance can lead to nonadherence, worsening ofthe illness, and, in some cases, death by suicide.

The Depression and Bipolar Support Alliance (DBSA),previously National Depressive and Manic-DepressiveAssociation, is the nation’s largest illness-specific, patient-directed organization. Incorporated in 1986 and headquar-tered in Chicago, Illinois, DBSA has a nationwide grass-roots network of more than 1000 support groups. It isguided by a 65-member Scientific Advisory Board com-prising the leading researchers and clinicians in the field ofmood disorders. DBSA’s bylaws mandate that at least51% of its Board of Directors be diagnosed with depres-sion or bipolar disorder, and more than half of its com-mittee members and staff live with a mood disorder. Theorganization has long been concerned with the problem oftreatment resistance—what causes it, what can be done,and how health care providers can help their patientsbecome empowered and well. Daily contact with peopleliving with mood disorders makes DBSA particularlyqualified to present a patient perspective of treatment-resistant depression.

The Realities of Treatment-ResistantDepression

For some people, treatment of depression is simple. Withproper medication and therapy, they are able to return tohigh levels of functioning without much delay; however, itis becoming evident that this type of rapid recovery is theexception rather than the rule. In a DBSA online survey ofnearly 1400 individuals who had been treated for depres-sion, one quarter of the respondents reported feeling nochange in their depression from the time of treatment onset

(Doh 1999). A DBSA survey of 1001 primary carepatients with depression revealed another disturbing sta-tistic: 78% reported that their depression had not beencompletely controlled during the two preceding months,even though many had been taking the same antidepres-sant for 3–5 years (DBSA 2000). Many of the onlinerespondents and 100% of the primary care patients weretaking medication at the time of the survey. This highoccurrence of partial response is troublesome.

It is imperative that health care professionals, families,friends, and the public understand the hopelessness anddemoralization felt by those who have tried treatment,sometimes numerous treatments, and not found relief.Nearly every day, DBSA receives descriptions like these:

“I want to live happily again, be successful in my career, havehealthy relationships with friends and family, and most of allI want to be a good mother to my son. I can’t do any of thisas well as I should with this depression holding me down.Please tell me you can help and that it’s not hopeless forpeople like me.”

“The problem is that my depression has never dissipatedfrom my life. I do not ever recall a period of time that I havenot been depressed. My psychiatrist suggested working witha psychologist to work on my depressive issues. My depres-sion is clearly not situational due to its longevity. Please donot suggest that I speak to my psychiatrist again regardingthese issues as I already have.… [My] questions … were notanswered to my satisfaction.”

“I have suffered from depression on and off for years. Ithink I have had it since I was a child.… In 1997, I sank intothe worst depression I ever felt.… My entire self, my soul,was hurting. Suicidal thoughts came—it was not so much thatI wanted to die but that I wanted to end the pain.”

There is a critical need for better medications and othertherapies for treating depression. Treatment-resistant de-pression has recently been receiving a tremendous amountof attention from pharmaceutical companies, scientific andmedical professionals, and other clinicians. The contribu-tions made in terms of understanding and treating depres-sion are recognized and appreciated, but it is important toremember that there is still a long way to go.

Research is by nature logical and mathematical, but itdoes not have to be unfeeling. Although research deals withchemicals and statistics, it also deals with real individualswho have genuine pain and frustration. Research and treat-ment will significantly improve if these people and theirfeelings, challenges, and needs are kept in mind.

© 2003 Society of Biological Psychiatry 0006-3223/03/$30.00doi:10.1016/S0006-3223(03)01789-4

Treatment-resistant depression can weigh heavily onpatients and their families. Being asked to wait 2–4 weeksor longer for medication to “kick in” or having toexperiment with two, three, or more medications beforefinding the one that provides some level of relief isfrustrating, demoralizing, and life-threatening. Strugglingwith untreated depression for long periods of time (inmany cases, years or even decades) exhausts patientsphysically and emotionally. It makes many doubt theirdoctors’ competence and makes them even less sure thereis a reason to go on living. Children with depression havebegged their mothers to kill them to end their suffering.Far too often, people stop seeking new treatment becauseit takes too much energy and their faith in doctors is lost.

Delayed Treatment, Lost Hope: SomeCauses of Treatment Resistance

Treatment-resistant depression results from a variety offactors. Although some of these factors are beyond doc-tors’ and patients’ control, others can be addressed withincreases in education and changes in attitudes. For somepeople, treatment resistance can be a result of depressionthat has been untreated for a long period of time. Becauseof the stigma associated with the illness and the wide-spread belief that a person can self-treat by “thinkingpositive,” many people are never diagnosed with depres-sion or wait years and years for treatment because they donot seek help. Given that symptoms of depression areexperienced in everyday life—for example, a person is sadwhen a parent dies, angry when he or she loses a job orsimply has “bad” days—depressive symptoms may not berecognized as warning signs of an illness. Many parentsare not aware that chronic irritability, rages that last forhours, and suicidal talk by young children can indicate thepresence of a treatable mood disorder rather than an attemptto “get attention.” So many people don’t realize that thesymptoms that have disrupted their lives and destroyed theirpersonal relationships are treatable (Dent 2000).

When depression remains untreated for too long, aperson’s bleak outlook can become reality. A person withuntreated or undertreated depression experiences a gray,often hopeless world and can easily forget the person he orshe was before the onset of the illness, or worse, neverknow the potential for true happiness. This is especiallytrue if that person comes from a family beset withdepression. Everyone needs models for living a joyouslife. If people observe very little joy as children, they maynot know it is something they deserve to experience asthey get older. When the world of depression is the onlyworld they know, it is difficult for them to detect the

illness of depression. And if they do, is it any wonder thatthey often settle for incomplete wellness?

Misdiagnosis: A Need for Better Screeningand More “Face Time”

Another significant barrier to successful treatment ofdepression is misdiagnosis. There is almost no possi-bility of wellness if people are treated for the wrongillness. For example, what an uninformed or time-strappedphysician might see as treatment-resistant depression mayactually be bipolar disorder. Sixty percent of people withbipolar disorder recently surveyed reported having beenmisdiagnosed with depression at least once (DBSA 2001). Abipolar disorder diagnosis should be ruled out beforebeginning treatment for depression.

A significant factor contributing to misdiagnosis is thatpeople are more likely to report depressive symptoms thanmanic symptoms. For example, although 75% of peoplewith bipolar disorder said they experienced heightenedmood, elation, and increased self-confidence, only 37%reported these symptoms to a physician (DBSA 2001). Itis imperative that more effective screening tools for maniabe developed—especially for children, the elderly, andminority populations—to lower the incidence of misdiag-nosis. In addition, primary care physicians need to bebetter educated on how to diagnose mania. When sur-veyed, 74% of primary care physicians reported it wasvery easy or somewhat easy to diagnose depression,whereas only 26% felt the same about diagnosing mania(DBSA 2000). DBSA believes it is because of this that44% of the physicians reported asking less than onequarter of their patients with depression about symptomsof mania (DBSA 2000).

It can take great perception on the part of a health careprovider to determine what is really happening with apatient. Unfortunately, perception requires the luxury oftime. The lack of physician “face time” with patientscontributes to poor diagnosis and treatment. In a DBSAsurvey of nearly 900 primary care physicians, 49% saidthe average length of an initial exam for the diagnosis ofdepression is 20 minutes or less (DBSA 2000). Thissurvey also revealed that more than half of the primarycare physicians reported seeing 23 patients on an averageday. Sixty percent of the physicians reported that at least10 of these 23 patients suffered from depression. Is it anywonder that little substantive dialogue takes place duringsuch patient–physician meetings? Despite the realities ofmanaged care, if mood disorders are to be properlydiagnosed and treated, more time needs to be spentdiagnosing them and developing the right treatment planfor each individual. An investment of time during the first

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visit can result in an immediate correct diagnosis andeffective treatment to prevent future crises.

Addressing Treatment Resistance withEducation and Communication

Physicians and consumer advocacy organizations mustsignificantly increase their efforts to educate patients andtheir families about identifying treatment-resistant depres-sion, avoiding it by adhering to treatment, and tryingvarious options if it is experienced. Before diagnosing adepression as difficult to treat, physicians first must becertain that the illness is truly nonresponsive to treatmentand that there are not other mitigating factors.

People must be encouraged to have patience, to givetheir medications time to work, and to learn that the effectsof antidepressants are not as quickly felt as when taking anaspirin or cold medication. Many people with depressiondo not know that changing a dosage or adding or substi-tuting a different class of medication might be moreefficacious for them. People need to understand that allantidepressants are not the same; that they work differ-ently in the brain, and that a lack of or a partial responseto one antidepressant does not mean that others won’twork.

Physicians and patients need to discuss side effectsopenly and completely. Before prescribing any medica-tion, the patient or parent should be made aware ofpotential side effects. Different patients prefer to cope withdifferent side effects, and only through frank communica-tion can the physician determine these preferences andmake effective medication decisions with the patient.Patients and parents also need to know what options areavailable for dealing with difficult side effects.

Although informed patients know that medications canbe added, dosages can be adjusted, and dosing times canbe changed, the majority don’t know these facts, and thenature of their illness makes them believe it is easier togive up. When the patient rules out the possibility thattreatment will help, he or she is in the most danger. Givinghope to a patient is one of the most powerful things aphysician can do.

Patients must also be made aware of medication inter-actions and learn that abusing drugs or alcohol will keepthem from getting well. Anyone with depression and asubstance or alcohol problem needs to understand thatthese are two separate illnesses. They require two separatetreatments that can and should work together. Takingantidepressant medication does not mean a person is “notsober,” and being in a recovery program does not mean aperson does not need treatment for depression.

There is also a paucity of knowledge about psychother-apy. Patients should know what to expect from psycho-therapy and what to do if progress isn’t made. People needto know that there are different types of psychotherapy andthat some are better for treating mood disorders thanothers. It is important that a patient and psychologist havepersonalities that work well together and that a patient isnot afraid to consider another psychologist if treatment isnot progressing as well as it should. Finally, it is criticalthe psychiatrist and psychologist be willing to consult todevelop the best treatment plan for the patient.

Empowerment: Encouraging SecondOpinions

Some people may not be difficult to treat, they may simplybe receiving the wrong treatment. They need to beempowered so they don’t hesitate to ask their doctors totake their unique needs into consideration. They must viewthemselves as equal partners in developing treatment plansand expect their physicians to do the same. Their physi-cians must seek out a more specific answer than “fine,”when they ask how the patient is feeling.

A recent survey of patients being treated for depressionin the primary care setting revealed a troubling disconnect.Although 71% of the physicians reported presenting alltreatment options to the patient for a collaborative deci-sion, only 54% of patients reported that they madecollaborative decisions with their doctors (DBSA 2000).Many people get second opinions for conditions such asheart disease or cancer, yet there is a reluctance to seekcounsel from another psychiatrist if treatment is not fullyeffective. Psychiatrists should urge second opinions. Inaddition, people rarely say to their physicians, “Doctor, Icould be doing better.” Patients often do not realize thatthere might be other treatment options to try. So many endup believing that depression is their lot in life—the hand ofcards they were dealt. As William Styron so accuratelywrote, they struggle through their days feeling “con-demned to life.”

Physicians, too, must remember not to give up hope.Although the practice of psychiatry can be challenging, nopatient wants to have, as one DBSA constituent did, adoctor throw up his or her hands and say, “Well, if thistreatment doesn’t work, I don’t have anything else foryou.” With the wealth of treatment options available andthe many trials underway to find new treatments, how cana patient be “out of options”? The patient may believe thisis true, but the last thing that patient needs is for the doctorto say so. If the doctor truly feels that way, it’s time toimmediately refer the patient elsewhere.

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Helping Someone with Treatment-ResistantDepression

What happens when individuals with mood disordersdon’t improve even after learning and trying all theiroptions? What about the person who just can’t seem to getbetter? What about the children or teenagers who do notrespond to treatment, as well as their families?

DBSA urges people with mood disorders and theirfamilies to be their own advocates, to be active in their ortheir child’s treatment plan, to form support systems, andto have no shame about their illnesses. It also recommendsthat patients partner with their physicians and exploreevery possible treatment option. DBSA advises people tobecome informed, to learn all they can about their ill-nesses. It assures people that they’re not alone, and that,just like them, many people are having trouble findingeffective treatment for depression. DBSA also urges peo-ple to find a qualified health care provider, one who hascurrent information, who does not carry stigmatizingbeliefs about depression, and who has time to listen aspatients hesitantly try to explain something they don’tunderstand and can’t quantitatively measure. And DBSAinforms people that collaborative, constructive relation-ships with their health care providers are possible, but onlywhen both are dedicated to making positive changes.

Making these suggestions as a third party can do little toimprove quality of life. If patients are suffering, they wantone thing and one thing only: to feel better right away. Thewillingness to “hang in there” can only be achievedthrough partnerships involving the patient, his or herfamily, and the health care provider.

The Need for Research

There is a need for increased attention to the developmentof new delivery systems for antidepressant medication.This could certainly increase adherence. And at the end ofthe day, after the informed consent forms, the institutionalreview boards, the statistics, the university politics, and thegrant writing, researchers and clinicians need to rememberthe person suffering. There seems to be significant com-petitiveness among mood disorder researchers; more col-laboration can only help uncover new treatments sooner.

DBSA understands that research discoveries arrive inbaby steps. It recognizes the stigma that goes with psy-chiatric research, the belief by many that behavioralresearch is not real science. DBSA even understands thatit may be years before the level of funding available formood disorders equals that for other illnesses that are farless common, far less costly to our society, and far lessdeadly. The fact that there were almost twice as manysuicides as homicides in 2000 (American Association of

Suicidology 1999) should be a resounding call to action, asshould the fact that depression is the number-one cause ofdisability in our country today (World Health Organiza-tion, no date). The DBSA believes stigma is responsiblefor the lack of sufficient emphasis on the undertreatmentof mood disorders and will continue emphasizing thedevastation that depression and bipolar disorder cause; itwill continue to advocate for increased funding andtargeted research.

Working Together for Better Outcomes

Patients need help from the pharmaceutical industry,research scientists, psychiatrists, and clinicians to meettheir needs: more effective medications, fewer side effects,ways to improve the benefits of psychotherapy, and bettereducation. DBSA urges all those who are professionallyconnected with mood disorders to become familiar withthe resources, service, and support that the organizationoffers. Because it is patient-focused, DBSA is particularlyqualified to make the experience of living with treatment-resistant depression understandable to physicians, mentalhealth practitioners, and managed care providers. A men-tal health care provider or researcher who doesn’t live withdepression can be greatly helped by gaining an under-standing of the illness from the patient’s point of view. Itmay be surprising to learn that after a patient perspectivepresentation at Harvard University, one young psychiatristsaid, “I never realized the importance of being kind.”Medical schools must realize the importance of teachingkindness, empathy, and patient partnerships.

Professional organizations can play a significant role inimproving treatment by increasing primary care education.For primary care physicians, learning to identify maniacan be immensely helpful in treating individuals withmood disorders to total wellness. Increasing physicianattention to the problems associated with dual diagnoses,and co-occurring and comorbid illnesses can save count-less lives.

Keeping Goals in Sight

Every year, tens of thousands of people with depression,including children as young as 8 years of age, take theirlives because their depression is too much to bear. Somany people desperately need to be given hope. Anyonewho has had a crushing depression that doesn’t remit foryears or who has sat with a sobbing child who has nofriends, can’t attend school, and asks why God made himor her so sad, can understand why it is so important to findnew solutions.

People need health care providers to understand that it isnot enough for patients to just stop crying all the time; they

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also want to have the energy to attend school or work andhave fulfilling personal lives. People need medicationsthat won’t make them impotent, trigger panic attacks,cause them to gain weight, or make them lethargic. Theyneed faster and longer acting medications to improveadherence. They need treatments that are significantlymore affordable. Patients deserve lives free enough frommisery that they want to live them. In the words of oneyoung woman, “The most important thing for people toknow is that even in your hardest times, there is more tolife than nothing at all. Life is a worthy challenge one mustalways meet.”

It is of utmost importance for physicians, mental healthpractitioners, legislators, the media, and managed careproviders to partner with patients to find new treatmentsand workable solutions. The Depression and BipolarSupport Alliance believes that people do not have to be“condemned to life” and that depression—especially un-treated depression—does not have to be a way of life.

Lydia LewisLaura Hoofnagle

Depression and Bipolar Support Alliance(Previously the National Depressive and Manic-

Depressive Association)730 North Franklin Street, Suite 501Chicago, IL 60610-7224

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Doh S (1999, August): On-line survey of 1,370 people treated fordepression within the last 5 years. New York, NY: KetchumResearch and Measurement Department.

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