(Similar to everything else, WIP)
How effective are our current treatments for depression?
Divergent Outcomes in Cognitive-Behavioral Therapy and Pharmacotherapy for Adult Depression
Cognitive-behavioral therapy (CBT) and pharmacotherapy are, on average, equally and moderately efficacious acute-phase treatments for unipolar depression. For example, 50%−60% of patients receiving CBT or pharmacotherapy for depression respond, compared with 40% receiving pill placebo, and the average CBT or pharmacotherapy patient has posttreatment symptom levels roughly 0.3 SD below those of patients receiving pill placebo. However, these favorable averages may obscure some patients’ negative outcomes. Moreover, beyond conventionally defined response (≥50% symptom reduction) and remission (posttreatment scores ≤7 on the Hamilton Depression Rating Scale [HAM-D]), only patients with unusually positive outcomes have no residual symptoms with attendant dysfunction.
Perhaps 5%−10% of psychotherapy patients show reliable deterioration (increases exceeding the symptom measure’s reliable change threshold), with evidence of higher risk among children than adults, in routine practice compared with randomized clinical trials, and in psychotherapy considered more broadly than CBT specifically.
“Reliable deterioration” was an increase meeting the p<0.05, two-tailed, change threshold of ≥8 points on the HAM-D (28) or ≥9 points on the BDI (29).
This found 40% of people have no response to CBT. If we subtract placebo from the “response” group, we find that CBT provides a demonstrable effect for only 20% of all patients. The average symptom decrease is relatively small for those who do respond. Among the non responders 5-10% are significantly harmed by “treatment”. Significantly harmed means a catastrophic increase in symptom severity.
Depression: How effective are antidepressants?
The various antidepressants have been compared in many studies. Overall, the commonly used tricyclic antidepressants (SSRIs and SNRIs) were found to be equally effective. Studies involving adults with moderate or severe depression have shown the following: Without antidepressants: About 20 to 40 out of 100 people who took a placebo noticed an improvement in their symptoms within six to eight weeks. With antidepressants: About 40 to 60 out of 100 people who took an antidepressant noticed an improvement in their symptoms within six to eight weeks. In other words, antidepressants improved symptoms in about an extra 20 out of 100 people.
20% of people receive an effect over placebo, and these are among the moderate to severe group. Adding the low severity group degrades this ratio further.
Psychotherapies for depression may be effective compared with control conditions, but more than half of patients receiving therapy do not respond and only one third remitted. More effective treatments and treatment strategies such as sequencing and combining treatments are clearly needed.
This study found more than 50% of people have no response to therapy. Therapy doesn’t even beat the coin flip, and that’s including placebo effect.
At 26 years after the formulation of a largely speculative hypothesis concerned with the iatrogenic effects of AD, the evidence I have reviewed indicates that use of these medications may have the potential to worsen long-term outcome of mood and anxiety disorders in individual cases. Similar mechanisms, subsumed under the concept of supersensitivity psychosis, may apply to the use of antipsychotics in schizophrenia and mood disorders. The oppositional model of tolerance is also consistent with the use of psychotropic medications as recreational drugs.
However, currently, prescriptions are driven by an overestimated consideration of potential benefits, little attention to the likelihood of responsiveness and neglect of potential vulnerabilities to the adverse effects of treatment.
Significant amounts of harm caused, overestimated benefit, and neglect of consideration of the harmful effects? This is going to be a meme I think.
How well are we tracking negative outcomes of therapies?
Negative effects of psychotherapies for adult depression: A meta-analysis of deterioration rates
Only 6% of all trials comparing psychotherapy with a control condition reported deterioration rates, using different ways to define deterioration which made pooling the prevalence rates across treatments and control groups impossible.
In the final analysis, the data on harms and burdens were rated as insufficient/low strength of evidence due to their limitations (e.g., potential for higher risk of bias due to study designs). However, given the central role of assessing the balance of benefits versus potential harms of a treatment in clinical practice guideline development, the relative lack of reporting potential harms in psychotherapy research and subsequent lowering of overall quality of the evidence is negatively impacting clinical practice guideline development. In order to be fully utilized in care, an understanding of not only the potential benefits of treatments, but also the potential harms and burdens of treatments are necessary for informed decision making. The current lack of consistent definitions of treatment harms and burdens and the paucity of data on the topic hamper the ability of guideline developers to create well-documented and supported recommendations and therefore limit the information providers and patients have to inform their decision making.
How would we know if psychotherapy were harmful?
Patients can be harmed by treatment or by the decisions that are made about those treatments. Although dramatic examples of harmful effects of psychotherapy have been reported, the full scope of the problem remains unclear. The field currently lacks consensus about how to detect harm and what to do about it when it occurs.
A series of studies by Lambert and his group subsequently determined that 35–40% of patients in randomized control trials do not improve over the course of therapy, and that among non-responders, 5–10% actually deteriorate, terminating treatment with higher levels of symptomatology. Lambert et al.’ work further studied therapists’ assessment of their patients’ outcomes and suggested that therapists are less likely to identify the occurrence of treatment failure than their patients. They also found that therapists are inclined to rate themselves as above-average clinicians and to underestimate the prevalence of deterioration among their patients.
We have more consilience here around the 5-10% negative outcome, but more shockingly we find that not only do negative outcomes rarely get tracked at all, we find significant clinician bias with regard to identifying those negative outcomes. Even worse, there is no current framework being used to identify instances of harm, nor any widely practiced harm reduction policy.
The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05).
It’s insane, these effect sizes absolutely dwarf the effect sizes supporting the use of these medications. We pull medications off the shelf for effect sizes far far smaller than this. Compare this to COVID vaccine effect rates!
Is research overstating the effectiveness of anti-depressant medications?
Response rate would be 56% for antidepressants and 40% for placebo, but mean change score would be 9.4 for both antidepressants and placebo. That is, mean improvement would not differ between drug and placebo arm!
When a specific patient shows improvements that are considerably larger than the average drug effect, then this symptom change is usually not brought about by the drug but rather by other factors, for example, the patient may have fell in love or he/she just had few good days due to random symptom fluctuations (Senn, 2018). Moreover, seeing a bimodal distribution (i.e. benefiters vs. non-benefiters) in the six graphs provided by Thase et al. requires a lot of imagination; in three graphs (b, c, and d) the distribution is obviously not bimodal.
Finally, the approach chosen by Hieronymus et al. to establish efficacy is misleading, as it merely compared d effect size estimates for single items to the full scale. Given that the depressed mood item is an ordinal variable with five levels, d is an inappropriate effect size estimate, as its calculation requires at least interval scale.
In addition, the stated ‘NNT of less than 3’ is evidently false. In the meta-analysis of Geddes et al. (quoted by Goodwin and Nutt), the relapse rate on placebo versus SSRI was 37% versus 15%, so the absolute risk reduction is 22%, which produces a NNT of 4.5.
Ooof. So this is a response to one of the most cited studies regarding anti-depressant efficacy. I actually think this piece is under-selling how bad the overstatement is.
The published data from RCTs on antidepressants for the treatment of major depression is compatible with a near-constant treatment effect. Although it is impossible to rule out a substantial treatment effect heterogeneity, its existence seems rather unlikely. Since the average treatment effect of antidepressants falls short of clinical relevance, the current prescribing practice should be re-evaluated.
Here we find that not only do most antidepressants fail to show clinically relevant effect, what we thought was heterogeneous individual effect was actually just placebo? And we can’t extract placebo effect because that would collapse evidence supporting the effectiveness of the drugs. No win situation here.
Individual response to antidepressants for depression in adults-a meta-analysis and simulation study
An analysis of the variability ratio does not allow for drawing conclusions on the individual level, and thus cannot distinguish between a potential treatment-by-patient interaction and that of a treatment-by-subgroup interaction. Yet, our results showing that the variance in the antidepressant group did not differ from the placebo group, may indicate that neither of those scenarios are likely.
Based on these data, we cannot reject the null hypothesis of equal variances in the antidepressant group and the placebo group. Given that RCTs cannot provide direct evidence for individual treatment effects, it may be most reasonable to assume that the average effect of antidepressants applies also to the individual patient.
Yet another study finding placebo drives nearly the entire effect of anti-depressant efficacy.
Thus, relapse-prevention RCTs likely confound the detection of their main outcome of interest: “relapse.” Using slower tapers, active placebo controls, and specific covariates in analyses would reduce the risk of withdrawal confounding, and better reporting would reduce the opaqueness of trials. The crisis in psychopharmacology is fueled partly by the disconnect between claims of therapeutic efficacy from so-called best-evidence methods despite unchanging population-level indicators of psychiatric sickness. Only by “stacking the deck” against trial sponsors’ hoped-for outcomes can psychopharmacology trials regain scientific credibility.
Would researchers shape studies designed to exclusively prove that these treatments are effective? Yes. Yes they would. And do.
The evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.
It’s a pretty consistent story isn’t it?
How did we do before the age of “modern” treatments?
Outcome of mood disorders before psychopharmacology: A systematic review
This review shows that the long-term outcome for patients with mood disorders in the predrug era was reasonably positive. Most patients recovered and the majority seemed to remain well after their recovery. Comparisons with modern drug-treated cohorts are difficult due to methodological limitations. Nevertheless there are some consistent findings. The length of mood episode has decreased significantly from around 1 year to 1 month or less. Death rates, other than those due to suicide, have also reduced significantly. In contrast, the recurrence of mood episodes appears to have significantly increased. These data, to paraphrase Dickson and Kendell (1986), provide no comfort for those, including ourselves, who have believed that drugs provide an effective prophylactic treatment for at least a substantial minority of patients with affective disorders.
They legit found ECT was more effective and generally safer than antidepressants. WOW.
Further Reading:
Four research papers I wish my GP had read before prescribing antidepressants
However, at that time, the Defeat Depression campaign had successfully created a narrative adopted by most prescribers, in which anxiety or depression were described to the patient as caused by a ‘chemical imbalance in the brain’ and that SSRIs were safe, effective, and non-addictive. Why would a doctor feel the need to do a full literature review?
The root of it all.
Anticholinergic drugs cause dementia, lead to worse outcomes than those not taking them.
Blindly following these models is not only ineffective at treating the mental health crisis today, it’s setting us up for a massive dementia bomb in the future.
— Still looking for pre paxil/prozac studies on depression remission, particularly longitudinal ones. Looks like the definitions of depression before the 1950’s were pretty all over the place, and didn’t really firm up until the DSM-III which was the dawn of the age of pharmacopeia.