No Benefit for Adding Antidepressants to CBT in Severe Depression

For those with severe depression, inpatient CBT was effective but the adding antidepressants did not improve treatment outcomes.

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In people hospitalized for severe depression, cognitive-behavioral therapy (CBT) was significantly effective, researchers write—and adding antidepressants (AD) didn’t improve outcomes. The researchers note that their finding contradicts the advice offered in clinical practice guidelines.

“The inpatient CBT was effective in depression. The effectiveness of CBT is not improved by the additional use of AD. The current prescribing practices of AD should be questioned,” they write.

The study was led by Reinhard Maß Kerstin Backhaus, Katharina Lohrer, Michael Szelies, and Bodo K. Unkelbach at the Center for Mental Health Marienheide, Germany. It was published in the journal Psychopharmacology.

Their participants came from the Aaron T. Beck inpatient unit at the Center for Mental Health Marienheide. The Beck unit is focused on providing CBT to all patients but also offers pharmacological intervention as needed, following a medical model of psychiatric treatment.

Several years ago, the Beck unit operated following the German guidelines, which recommend combining antidepressants with psychotherapy for severe, chronic, or recurrent depression. However, after a 2019 study revealed that the patients who received antidepressants did no better than those who did not, the unit’s policy changed—only those who specifically requested antidepressants were considered for those drugs. (All patients continue to receive CBT.)

Thus, the researchers were able to conduct this study by comparing outcomes from the previous years (Phase A, in which 60.3% of patients were prescribed antidepressants by the time they left the unit) with more recent outcomes (Phase B, in which only 27.9% of patients were prescribed antidepressants).

Unlike clinical trials, which typically have stringent criteria for participants—often excluding those with suicidal thoughts, those with severe or recurrent depression, and those with other mental health problems—the current study included a much more realistic group of patients. That’s because the participants comprised the actual patients treated in the Beck unit during this time. All the participants had depression severe enough to require hospitalization, with features such as a high risk of suicide, inability to work, and having had ineffective outpatient treatment already. Many patients had comorbid conditions, such as anxiety (about 20%), personality disorders (about 20%), OCD, eating disorders, psychosis, or PTSD (about 16% combined).

Thus, this study tells us what treatment works for real-life patients who are being treated in an inpatient hospital setting.

To measure depression severity, the researchers compared scores on the Beck Depression Inventory (BDI-II). The average score on the BDI was the same for both groups, as was the number of people who “responded” to treatment (their BDI score decreased by at least 50%) and the number of people who “remitted” (BDI score of 12 points or less). This was true both at the time the patients left the inpatient unit, as well as at the six-month follow-up.

In both groups—whether patients received an antidepressant plus CBT or CBT alone—a little more than 70% found the treatment to be effective (responded or remitted by the time they left treatment). After six months, this number dropped somewhat—closer to 50%—but remained similar in both groups.

And again, this is for patients hospitalized with the highest depression severity, suicidality, and other mental health problems at the same time.

The researchers sum up their results:

“At discharge (T2), there were 28.4% non-responders, 16.0% responders, and 55.6% remitted patients in phase A, and 28.3% non-responders, 14.8% responders, and 56.9% remitted patients in phase B (χ2 = 0.239, df = 2, p = 0.887). At follow-up (T3), there were 49.7% non-responders, 8.8% responders, and 41.5% remitted patients in phase A, and 48.8% non-responders, 12.3% responders, and 38.9% remitted patients in phase B (χ2 = 1.945, df = 2, p = 0.378).”

Four patients died by suicide during Phase A. All four were taking antidepressant drugs. No patients died by suicide during Phase B.

These outcomes demonstrate that whether patients received an antidepressant or not, they generally improved with CBT, and most of them maintained that improvement at six months. Some further analyses added preliminary evidence that the CBT-alone condition was slightly better than the combined condition: In the CBT-alone condition, treatment time was shorter, there were fewer dropouts, and the effect size for the decreased depression scores was higher.

“Some superiority of treatment is evident in phase B: (1) The treatments in phase B were 4½ days shorter; (2) in phase A, the proportion of dropout was greater than in phase B; (2) phase B shows somewhat higher effect sizes for the decreases in depression at T2 and T3,” the researchers explain.

The researchers write that their finding is consistent with other studies, including a large 2023 meta-analysis that found CBT alone was just as good as combined therapy.

One limitation of the study may involve the expectation effect: Patients who decide to go to the Aaron T. Beck inpatient unit know that they will receive psychotherapy and are likely to believe that it will help them. This may differ from patients in other units, who may not have that belief. It may also vary by country—it’s possible that patients in the US don’t have as high an opinion of CBT and thus wouldn’t get the boost from having positive expectations. It’s also possible that a hospital inexperienced in CBT might do a worse job at psychotherapy than the Beck unit, which specializes in that approach.

However, the researchers also mention that the slight benefit of antidepressants over placebo seen in clinical trials may be due to the methodological flaws of those studies. They cite the recent finding that only about 15% of patients may experience a unique benefit from antidepressant drugs—and note that even that could be due to the breaking of the blind in drug trials.

“In general, significant methodological problems have been highlighted in AD efficacy trials. A major problem is the breaking of the double-blind condition in RCTs which seriously questions the validity of these studies. Stone et al. pointed out that the 15% proportion of patients who seem to have a pharmacological benefit could also be explained by the effects of functional unblinding,” the researchers write.

CBT alone has been found to be just as effective as antidepressants in the short term and better than drugs in the long term. Moreover, psychotherapy avoids the harmful effects of antidepressant drugs, including sexual dysfunction for up to 88% of those taking them, weight gain and metabolic problems, emotional numbing, and more. Psychotherapy also doesn’t cause withdrawal, which is common after stopping antidepressants and can be long-lasting and severe.

Studies have found that antidepressant drugs may actually worsen outcomes in the long term, even after controlling for the baseline level of depression severity.

And one study found that those with more severe depression, those with comorbid anxiety, and those who were suicidal were least likely to benefit from antidepressant drugs.

The researchers in the current study write that clinical practice guidelines should be updated to reflect the lack of benefit for add-on antidepressant treatment. However, they note that this is unlikely because authors with financial ties to the pharmaceutical industry craft the guidelines.

“The treatment guidelines should therefore be updated accordingly. However, this could be hindered by the fact that many authors of the guideline have financial relationships with the pharmaceutical industry. This fact leads to a mixture of scientific and commercial perspectives and has been repeatedly subjected to severe criticism,” they write.

 

 

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Maß, R,. Backhaus, K., Lohrer, K., Szelies, M., & Unkelbach, B. K. (2023). No benefit of antidepressants in inpatient treatment of depression. A longitudinal, quasi‑experimental field study. Psychopharmacology. https://doi.org/10.1007/s00213-023-06417-4 (Link)

7 COMMENTS

  1. “The researchers in the current study write that clinical practice guidelines should be updated to reflect the lack of benefit for add-on antidepressant treatment.”

    Most definitely, the psychologists should stop behaving as a funnel into psychiatry, as they’ve behaved for many decades … at least if they want to maintain any semblance of respectability.

    Since the psychiatric DSM “bible” of so called “mental illnesses” was debunked as scientific fraud, over ten years ago.

    https://psychrights.org/2013/130429NIMHTransformingDiagnosis.htm

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  2. And I guess that SSRIs by at least decreasing insight, promoting emotional numbness, impulsivity and less care for others might actually be counterproductive to psychotherapy. Except, sarcastically, dialectic therapy, it might spice things a little bit there…
    That and the change in “baseline” behaviour, like being the therapist, now you have a somewhat new, different patient. Hum!? scratching me freudian beard…

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  3. Rereading the reference here to https://www.madinamerica.com/2023/01/therapy-beats-drugs-depression-long-term-outcomes/
    I have to back track a bit after noticing:
    “Notably, these numbers mean that more than half of the participants (58%) did not respond to therapy, and two-thirds of the participants (64%) still met the criteria for depression after therapy.”
    In “…the largest meta-analysis of a specific therapy ever conducted…”
    So, especulating, not denying the value of CBT, being skeptical, not advising nor analysing. But, maybe, somehow the whole thing of seeing depression as a disease might make it longer lasting?. More severe?. At least in some cases, not the really really bad ones.
    Not minimizing, nor suggesting ANYONE should do ANYTHING, nor change their BELIEFS, but if it were JUST me, maybe the thought: “Nah, it’s just a scratch, lucky it was just that. I just need to be more aware and carefull.” might make ME feel better?. Maybe even avoid depression or being labeled as such.
    Maybe the difference to control or placebo is more akin to not having the exorcism that, fantasizing, I require, and just for that I keep feeling bad about my suffering?. Even if I don’t need it at all or is counterproductive?.
    And in this review, and maybe others, maybe returning to the circumstances that caused the “depression” is the relevant factor? Hence the decreasing benefit over time?. Like in I need more than just talking and accept what I cannot change and have courage, wisdom, patience, persistance, learning and kidness, even illumination, to change what I can?.
    I can imagine how even that thought might be burdensome for me in some circumstances. Particularly when I am exhausted of struggling so much and I just need a place and time to crash and rest, see the thing differently, have some support, etc. Not trying to make anyone feel worse though.
    Like neither drugs nor psych therapy addresses the cause, or the perpetuating factor of the depression.
    Regardless that by giving the impression that it requires a specific treatment that you don’t get, or you are not getting any more, perpetuates not feeling well? even more or continuous suffering?. Like being called to return to a situation that made you feel “improved or improving” just talking about MY problems. And not MY friend’s, MY priest’s, MY “club”, MY community, MY world, etc., or deal with their other human qualities that at some point I just can’t deal with. Just the judegemntless me, me, me, when I can’t temporarily do anyone elses.
    Which could to my mind explain why psychoteraphy apparently is better than talking to good friends, priests, etc. Because people, maybe, by way of culture, discourse and expectations BELIEVE that should and would make then feel better?. And DO NOT expect that kind of benefit with the other interventions?. Like pampering a placebo effect with words like: “This is a very powerfull medication. It might make you feel dizzy a little bit. Take it it with a lot of water so it doesn’t irritate your stomach. Some tingling, somewhere, might happen, it’s normal, it goes away and it means the medication is working.” When it is no more than tiny amounts of sugar.
    And actually, I remember, somehow, I read somewhere that’s what old docs used to say, sometimes, when using actual pacebos.
    How does one make a control of that in research? Sounds to me like doing controlled RANDOMISED experiments in history.
    And benefits also not unlike mysthical, religious, trance or cuasitrance experience in some practices?. Predisposition to get “better” or “feel” something with something. Just the expectation of seeing an old dear friend makes me giddy, and might make my week, even my month!.
    Like the difference between going to dinner with the inlaws expecting the best or…
    So expecting psychotherapy to help and other things to do not, might be an uncontrollable variable in research at this time and “epoch”, AF, after Freud. Particularly when the therapist actually manages not to “dump” his or her issues on me when I actually cannot deal with them. Unlike, sometimes ME and my friends, priest, etc., the old reciprocity thing. And the hail Maries, do penitence, stay away from the evil one, r just the “do the dishes and walk the dog TOMORROW”, when I actually never wanted to have a dog. Just being facetious :).
    Which a therapist should never do, I imagine. Him or her should look stoic, knowledgeable, smart, caring, funny and… unbothersome. Unlike ME and yarayarayarah…

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  4. Just a comment on CBT and its alliance to the medical model. In the article depression is defined as: “a response to acute and chronic psychosocial stresses (e.g., workload, partnership problems, or interpersonal conflicts) combined with specific vulnerabilities (e.g., dysfunctional cognitive beliefs, deficits of social or emotional competence, or somatic problems) that lead to decompensation.” Note how the issue is localised with the individual almost as if to say that should people not have these “vulnerabilities” psychosocial stressors would not make them depressed, or said differently, they just need “better coping mechanisms”. The simplicity of this kind of thinking is alluring.

    Perhaps also some honesty when reporting results. Instead of saying “CBT is effective for depression” rather state that when we ask participants to self-report within the narrow scope of the Beck Depression Inventory on their experiences a certain percentage of the sample produced lower scores. We do not know if their quality of life has improved whatsoever.

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    • Those points you raise are very good ones. Paraphrasing hopefully correctly: labeling difference as a vulnerability and the lack of quality of like meassurement. I guess, following that narrative the study should have actually meassured if psycotherapy actually “improved” the stressors (being sarcastic) or “dysfunctional cognitive beliefs, deficits of social or emotional competence, or somatic problems” (being methodologically congruous). Like meassuring an antihipertensive dffect to claim that the reduction in blood pressure actually increases life-span.
      And just making you better “adapted” to stressors sounds to me a bit callous, like saying: “you need to get more resilient when people beat you” instead of: “People should stop beating you”. Like that approach in itself, seen that way, might cause hopelessness, at least at some point, i.e., before resignation.

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  5. Taking an Abilify was the nutritional equivalent to eating three slices of cheesecake. These things make you overweight (which is what cheesecake does to me), they elevate your heart rate, and cause you to become agitated and to behave irrationally after a brief period of sedation or “feeling better”, which is the ultimate goal of psychiatry: to make people FEEL better. Never to LIVE better. Our problems never go away, and our mental and physical health continue to decline.

    The line these psycho-bobbleheads spew is that these medications “take time to work”. While I’m being patient for my mind to get better, without addressing any of the comorbid issues in my life that are causing me psychological distress in the first place, my brain and my body are begging me to stop taking these things.

    People need to put two and two together. If you’re going to pop a Xanax to cope with the problems in your life then how is this any different from consuming alcohol or narcotics? Because the person prescribing you your drugs has a PhD and asks you how you’re doing?

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  6. First and foremost psychiatry torture is unacceptable. – it inflicts high levels and types of harm. Destroys. Can even kill.

    Then moving on to about CBT:
    I had a few sessions of CBT. It was not helpful to me. I never had heard of it before. As they were teaching what it was, it was not applying to my personal circumstances. It was “group” sessions. I listened and thought about it and replied that I believe that can apply in particular types of experiences; i.e. if someone is enjoying being rude to you or attempting to degrade you purposely, hurting you with words or however, you can obviously get hurt and keep getting deeper in hurt. However if you realize that what that person is doing is really that hurtful person’s problem and not yours, you can rethink how you are reacting emotionally. You may even be able to diffuse it some by reacting to them with smiling at them and being polite and telling them to have a nice day and just let their words slide off your shoulder and back onto theirs. Probably in events even more seriously harmful to you, you could accomplish that in a similar way. (but really this has always been good advice known in those type of circumstances. It wasn’t the “CBT thing” as such which is based on pure nonsense and ridiculous where it was attempted to apply it).

    If we are talking about totally different types of events, i.e. about an event that is very traumatic and it was actually the way it was, let’s say a horrific happening, i.e. witnessing severe horrific harm or horrific death, or something along those lines, and if you have feelings and you are not a robot, then that is going to cause severe pain in you as well, especially if it’s a loved one. You cannot change what happened, and you also cannot rethink it into candy coating it or rethink it into something other than it was just so you can lessen your pain. It may work for some people to pretend to themselves or to avoid it so their emotions can react differently, but realty is realty. Also it would be minimizing the horror the loved one went through and minimizing their worth, and in my opinion that would add to the pain.

    The heart and mind cannot be disconnected. We are not parts of a robot.

    My opinion is in order to try and heal or help another to heal, there has to be honesty (by all) about what happened and then go from there. That seems to be missing in any “treatments” out there.

    Drugs certainly are not the answer, and I could go on a lot about that. It is ridiculous that drugs are pushed the way they are. Deadly.

    We cannot pretend we are not sentient beings. I would hate to think what life would be like without being sentient beings, and all the sentient beings. It wouldn’t be life. We just have to figure out the appropriate ways to deal with the real legitimate deeply painful things in a realistic way because, simply, it is real. We cannot solve real pain with fake remedies.

    It is not as someone wrote “we inflict ‘all’ pain on ourselves, and we can adjust ourselves from doing it”. As in cold heart…cold mind, cold mind…cold heart?

    The most reasonable healing possibility is: honesty, reality of it, and “be your own therapist”. (even if and when it might have to go along with some help (but “appropriate” help)).

    “Be true to yourself”

    “Heal thyself”.

    “In times of trouble” “there will be an answer” JPM

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