Tag: PHQ-9

06/13/23

Overdiagnosing Depression with the PHQ

© lightwise | 123rf.com

According to PsychCentral, in 2020 there were more than 252 million prescriptions prescribed for mental health conditions. The total cost spent on psychiatric medications was more than $15.6 trillion. Zoloft (sertraline) was the most prescribed psychiatric medication with 38.22 million prescriptions, but only made Pfizer $523 million. This is because Pfizer’s patent on Zoloft expired in June of 2006. In its last full year of patent exclusivity, Pfizer’s sales for Zoloft totaled $3.3 billion. And it seems Zoloft’s popularity as an antidepressant can be credited at least in part to the introduction of the Patient Health Questionnaire (PHQ-9), which was developed by Pfizer shortly after Zoloft came on the market.

Writing for Insider, Hilary Bruek said Pfizer was persuaded to invest in the research necessary to develop what became the PHQ-9 by Howard Kroplick, one of their marketers. Kroplick told STAT: “It wouldn’t have happened if it wasn’t for me.” The PHQ-9 became a quick and easy tool that made many primary care doctors more comfortable prescribing antidepressants. Once Pfizer decided to underwrite the development of the PHQ-9, they contracted with Robert Spitzer and his wife Janet Williams, who were central figures in the revisions of the DSM-III.

In September of 2001, Kurt Kroenke, Robert Spitzer and Janet Williams published “The PHQ-9” in the Journal of General Medicine. The authors thought brief measures like the PHQ-9 were more likely to be used in the busy setting of primary care clinical practice. “Brevity coupled with its construct and criterion validity makes the PHQ-9 an attractive, dual-purpose instrument for making diagnoses and assessing severity of depressive disorders.” Note that the creators of the nine item PHQ-9 thought it could be used to diagnose depression. STAT reported the PHQ-9 has become an omnipresent tool, being cited in more than 11,000 scientific papers and routinely used in primary care and other routine visits.

Prescribing antidepressants in primary care based upon a PHQ-9 score of 10 or greater appears to be a sensible medical decision. There have been multiple studies such as Moriarty et al in General Hospital Psychiatry, that find the cutoff point of 10 on the PHQ-9 to have “acceptable diagnostic properties” for major depression. Studies, such as Negeri et al in the BMJ find the PHQ-9 has a combined sensitivity of 85% at the standard cutoff value of ≥10. A referral to a psychiatrist to confirm a depression diagnosis means a delay in treatment, meaning a delay in prescribing an antidepressant. Why not just recommend to the patient that they try a SSRI if their PHQ-9 score is equal to or greater than 10?

Malpass et al noted their concern that self-administered questionnaires like the PHQ-9 were regularly used in clinical practice to guide prescribing or to measure recovery and response to treatment. They thought when patients were given the PHQ-9, they were not interpreting the question items in the same way. They used a research technique called cognitive interviewing to identify ‘interpretive measurement error’ (IME). They found a wide range of comprehension and answer-mapping difficulties on the PHQ-9 that persisted over time.

Clinicians have expressed uncertainty about the PHQ-9’s validity and utility, and in the management and diagnosis of depression within primary care have a strong preference for clinical judgement over scores on severity measures. In light of the numerous ways the PHQ-9 may be missing the presence and/or intensity of certain symptoms that are meaningful to patients, clinicians should continue to adopt caution when using and interpreting questionnaire scores. The study raises the question that longer assessments may be better in providing opportunities for distinguishing frequency and severity.

Writing for Mad in America, Peter Simons commented on a meta-analysis study by researchers in the Journal of Epidemiology that concluded the PHQ-9 did not accurately estimate the prevalence of depression. The researchers concluded that that the PHQ-9 “substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies.” Simons said they found it was twice as likely to diagnose depression as the SCID, a semi-structured interview guide for making diagnoses according to the diagnostic criteria published in the DSM. 24.6% of participants in the study were found to be depressed by the PHQ-9, while only 12.1% met the criteria for depression on the SCID.

In primary care settings doctors will likely consider a positive score of ten or higher (the standard cut-off for depression screening with the PHQ-9) as indicating the presence of depression and consider it good enough to diagnose patients with depression and recommend antidepressant treatment. “This could lead to massive inflation of the estimates of how many people ‘have’ depression in the population.” The PHQ-9 is technically not a diagnostic measure of depression (despite what its creators said), but when it is used that way, the result is overdiagnosis.

Estimates of depression prevalence should be based on validated diagnostic interviews designed for determining case status; users should evaluate published reports of depression prevalence to ensure that they are based on methods intended to classify major depression.

The bottom line is that when screening tools like the PHQ-9 are used alone to assess depression in a person, clinicians are likely to misdiagnose it. And there are additional problems if the misdiagnosed person begins using an antidepressant to “treat” this so-called depression.

The general public widely believes depression is the result of a chemical imbalance, which shapes how people understand their moods. It may also discourage them from discontinuing a prescribed antidepressant medication, potentially leading to lifelong dependence on these drugs. An umbrella study by Moncrieff et al found “there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.” The researchers said most studies did not find evidence of reduced serotonin activity in people with depression when they were compared to people without depression. The chemical imbalance theory of depression is now seen as an urban legend, “never a theory seriously propounded by well-informed psychiatrists,” according to pro-medication psychiatrist Ronald Pies.

Moncrieff and others have also noted there are adverse effects from taking antidepressants. In “Persistent adverse effects of antidepressants, she said we are not clear about the nature of the neurochemical and physiological changes that occur when we take an antidepressant. “We are even less certain about how the body, including the brain, adapts to the long-term presence of these drugs.” We also do not know whether the changes produced by the drugs in the brain return to normal when the drugs are stopped; or if the changes persist.

Moncrieff then pointed to the withdrawal effects with long-term antidepressant use. She said the evidence suggests a picture similar to benzodiazepine withdrawal. There is a range of duration and intensity, where not everyone experiences noticeable or debilitating symptoms, but there are numerous reports of “withdrawal symptoms being severe and protracted.”

Moncrieff also referred to a 2006 article by David Healy and others that associated antidepressants and violence in some individuals. Healy said mechanisms that linked antidepressant treatment (rather than the depression itself) to violent behavior included akathisia, emotional disinhibition, emotional blunting, and manic or psychotic reactions. “There is good evidence that antidepressant treatment can induce problems such as these and a prima facie case that akathisia, emotional blunting, and manic or psychotic reactions might lead to violence.”

A group of researchers from the Nordic Cochrane Center in Denmark, including Peter Gøtzsche, published a meta-analysis in 2016 that confirmed Healy et al’s findings, according to Moncrieff. They found the risk of aggressive behavior doubled with the use of antidepressants. They also said akathisia was under-reported. Although akathisia occurred more often with study participants who used antidepressants, the difference was not significant. While they found no significant differences in mortality or suicidality, “our data confirmed the increased risk of suicide in children and adolescents.”

A 2016 literature review of long-term newer antidepressant use (SSRIs and SNRIs) by Carvalho et al noted over 12 adverse effects from antidepressants, that included weight gain, bleeding, sleep disturbance, diabetes, osteoporosis and others. The findings of this review suggest that long-term treatment with SSRIs and SNRIs “should be avoided if alternative treatments are available.” The authors noted there is a tendency to extend antidepressant treatment for long periods of time, believing that it protects against recurrence. However, that was not true in all cases. “This finding indicates that in patients with chronic recurring MDD, recurrences are difficult to prevent with [antidepressant] use only.”

It seems that the PHQ-9 depression scale has contributed to the overdiagnosis of depression and the overuse of antidepressants. One might even suggest this was exactly what it was developed to do. The PHQ-9 helped Pfizer (and eventually other pharmaceutical drug companies) reach into the untapped market of primary care physicians and gave them a tool they felt comfortable using in order to prescribe antidepressants to their patients. Unfortunately for the PHQ-9, the evidence that antidepressants have limited efficacy and multiple adverse side effects is growing.

09/1/17

Circle the Pfizer Wagons

© Darin Burks | 123rf.com

The U.S. Preventive Services Task Force (USPSTF) recommended that all adults, including pregnant women and women who have recently given birth, be screened in primary care settings for depression. The screening would be done by: general practitioners, family physicians, nurse practitioners or physician assistants. USPSTF said screening adults for depression in primary care settings was accurate, it was effective in relieving depressive symptoms and the likelihood of harm from screening and treatment was small. The problem is that over 60% of individuals diagnosed with depression in primary care did not meet the DSM criteria for major depressive disorder. This rises to 80% with individuals over 65.

Albert Siu and the USPSTF published “Screening for Depression in Adults” in the January 2016 issue of JAMA. The authors said: “The USPSTF found convincing evidence that treatment of adults and older adults with depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.” Commonly used screening instruments included the Patient Health Questionnaire (PHQ) in its various forms, as well as several others. But the USPSTF did not believe these instruments were getting as many false positives as noted above. “The accuracy of screening tests in the general adult population was established in the 2002 and 2009 USPSTF reviews and found to be convincing.”

Psychiatrist Vivek Datta pointed out the USPSTF guidelines did recommend that screening occurred when there were “adequate systems in place” for further evaluation and treatment. However, “55% of all US counties do not have a single mental health provider.” He noted that many of the symptoms screened for are nebulous and include “symptoms that are quite common in the general population and do not necessarily indicate a mental disorder requiring treatment.” They could represent the effects of a chronic medical problem. Moods are influenced by a variety of factors, such as our level of physical activity, what we eat, our financial security, alcohol and drug use, to name a few.

Symptoms of depression can occur as a result of lifestyle factors, substance use, medical illness, life events, interpersonal difficulties, and as a consequence of wider social policies. Comprehensive assessment frequently does not occur because of the lack of adequate services for those with mental health problems. The recommendation to screen all adults for depression ignores the social matrix in which depression occurs, will lead to further overdiagnosis and overtreatment of minor morbid mental states, and further overburden mental health services.

“A Glut of Antidepressants” was published on August 12, 2013, in The New York Times. It mentioned an April 2013 study published in the journal Psychotherapy and Psychosomatics that found almost 62% of 5,639 individuals “who had been given a diagnosis of depression within the previous 12 months did not meet the criteria for major depressive episode.” Several other studies have reported that: “diagnostic accuracy is low in general practice offices.” The study’s lead author said: “The vast majority of individuals diagnosed with depression, rightly or wrongly, were given medication.” Doctors must resist the temptation “to take out the prescription pad and write down an antidepressant and hand it to the patient.”

The NYT article did indicate that not only are doctors prescribing more medication, their patients are demanding it more. I think this is a likely an outcome of the decision to permit direct-to-the-consumer advertising for pharmaceuticals in 1997. See “Pharma and Advertising” or “Not Everything is As It Appears” for more on this topic. If anything at all was done to “confirm” the patient’s or doctor’s impression that there was a depressed mood state, using a quick screening instrument seems likely given the short time period most patients spend with medical staff in a primary care setting.

James Davies, the co-founder of the Council for Evidence-Based Psychiatry, wrote “The Sedated Society,” where he commented on how a BBC radio program had failed to mention the problem with the PHQ-9 (mentioned above) and the GAD-7, which he said are two of the most powerful questionnaires in the NHS (National Health Service). He said they have been used throughout the primary care system in the UK to assess whether or not a person has depression or anxiety. He said: “They set a very low bar for what constitutes having a form of depression or anxiety for which a drug should be prescribed.” He said the tens of millions of people who filled out these screening questionnaires don’t know that Pfizer Pharmaceuticals paid for their development and continues to hold the copyright for them. Their distribution throughout the NHS was paid for by Pfizer, which incidentally makes two of the most prescribed antidepressant and anti-anxiety drugs in the UK.

Although the BBC didn’t get Davies’s message out about the PHQ-9 and GAD-7, several news outlets did. At Vice, Hannah Ewens said “a few of us in the office” took the test, with everyone except one person got at least a score of mild depression. She personally scored within the “moderately severe depression” range, but doesn’t have depression at the moment. “If I have trouble sleeping ‘on several days’ or ‘nearly every day’ that bumps up my score significantly. And herein lies the problem: all of the indicators are symptoms of a modern lifestyle as well as signals of depression.” Ewens added that James Davies believes reliance on these questionnaires is becoming too commonplace because GPs don’t have the time to do proper interviews.

The Telegraph, another UK media outlet, echoed the Davies concern that the threshold for identifying possible depression was too low. Henry Bodkin noted that a PHQ chart was likely present in almost every GP consulting room over the last 20 years. He also said critics like Davies have said the GAD-7, also developed by Pfizer to screen for anxiety, sets the diagnosis bar too low. “These forms have a very low criteria for anxiety and depression. . . . Millions of people have filled them in and got medication, but did they know they were developed by Pfizer?”

Pfizer enlisted two “rock stars” in the field of psychiatric diagnosis to develop the PHQ-9 and GAD-7: Robert Spitzer and Janet Williams. Spitzer was the chairperson for the seminal changes incorporated into the DSM-III. Originally Williams was his text editor; later she became his wife and collaborator. Listen to an All Things Considered broadcast on Spitzer and the DSM, “The Man Behind Psychiatry’s Diagnostic Manual.”

In the September of 2001 issue of the Journal of General Internal Medicine, Kurt Kroenke, Robert Spitzer and Janet Williams published “The PHQ-9.” Their article examined “the validity of a brief, new measure of depression severity” called the PHQ-9. They concluded that data from their two studies provided “strong evidence for the validity of the PHQ-9 as a brief measure of depression severity.” Kroneke et al. also said brief measures were more likely to be used in the busy setting the typical medical practice. The brevity of the PHQ-9 was thought to make it “an attractive, dual-purpose instrument for making diagnoses and assessing severity of depressive disorders.” The Acknowledgements section said the development of the PHQ-9 was underwritten by an educational grant from Pfizer US Pharmaceuticals. Scrolling down further you’ll see:

From the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ). The PHQ was developed by Drs. Robert L. Spitzer, Janet BW Williams, Kurt Kroenke, and colleagues. . . . PRIME-MD is a trademark of Pfizer Inc. Copyright 1999 Pfizer Inc.

Then in the May 2006 issue of JAMA Internal Medicine, the same three authors introduced the GAD-7, a brief self-report scale to identify generalized anxiety disorder (GAD). Not surprisingly, they concluded: “The GAD-7 is a valid and effective tool for screening for GAD and assessing its severity in clinical practice and research.” They expected the GAD-7 to have “considerable utility in busy mental health settings and clinical research.” Once again is an acknowledgement that the development of the GAD-7 was underwritten by an unrestricted educational grant from Pfizer Inc.

If you want to see or use copies of these scales, Pfizer’s lawyers have been clearly involved in dialing back the company’s responsibilities if the scales don’t live up to their creator’s optimistic expectations. On the Pfizer website, on the “Terms of Use” page for the two scales, is the following. Pfizer said since the questionnaires relied on patient self-report, all responses should be verified by the clinician. A definitive diagnosis should be made on clinical grounds, “taking into account how well the patient understood the questionnaire, as well as other relevant information from the patient.” Diagnoses should rule out normal bereavement, Bipolar Disorder, and other potential causes of depressive symptoms. Then there is the following disclaimer. The “all caps” formatting is in the original.

PFIZER MAKES NO WARRANTIES OR REPRESENTATIONS OF ANY KIND AS TO THE ACCURACY, CURRENCY, OR COMPLETENESS OF THE INFORMATION ACCESSED AND USED THROUGH THIS WEB SITE.
YOU AGREE THAT ACCESS TO AND USE OF THE PHQ AND GAD-7 SCREENERS IS AT YOUR OWN RISK. PFIZER DISCLAIMS ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. NEITHER PFIZER NOR ANY PARTY INVOLVED IN CREATING, PRODUCING, OR DELIVERING THE PHQ/GAD-7 SHALL BE LIABLE FOR ANY DAMAGES, INCLUDING WITHOUT LIMITATION, DIRECT, INCIDENTAL, CONSEQUENTIAL, INDIRECT, OR PUNITIVE DAMAGES, ARISING OUT OF ACCESS TO, USE OF OR INABILITY TO USE THE PHQ/GAD-7, OR ANY ERRORS OR OMISSIONS IN THE CONTENT THEREOF.

The rhetoric about the GAD-7 and PHQ-9 and its variations related by their creators, Spitzer, Williamson and Kroneke seems to have been negated by Pfizer. Instead of the PHQ-9 being “an attractive, dual-purpose instrument for making diagnoses and assessing severity of depressive disorders” and the GAD-7 being “a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research,” Pfizer disclaimed all warranties expressed or implied for a particular purpose. Pfizer nor any party involved in creating the PHQ/GAD-7 will be liable for any damages from access or use of these questionnaires. Any users access and use the PHQ and GAD-7 does so “at your own risk.”

It seems that Pfizer circled their wagons to avoid any corporate liability coming from the use of these questionnaires despite the fact they paid for their development and continue to market them aggressively to general practitioners in the US and the UK. But the potential for the over diagnosis and over treatment of depression through the PHQ-9 has now reached a new height. Psychiatry Advisor reported in August of 2017 that Google announced whenever someone searches for ‘clinical depression,’ they have an option to take the PHQ-9. Google partnered with NAMI, the National Alliance on Mental Illness, to make depression screening with the PHQ-9 part of searching for ‘depression’ on the site. NAMI said: “We hope that by making this information available on Google, more people will become aware of depression and seek treatment to recover and improve their quality of life.”

So where did all that effort with the PHQ-9 and GAD-7 get Pfizer? Pfizer currently hold the rights to the brand rights for Xanax (alprazolam), an anti-anxiety drug, and Zoloft (sertraline), an antidepressant. Both have been available as generics for a number of years. And although The Telegraph article didn’t name Pfizer’s top selling antidepressant and anti-anxiety drugs in the UK, they must be the same two. Up-to-date yearly sales data for psychiatric drugs is hard to come by, unless you pay an organization like IMS for access to their sales data. But there is data available from 2013.

IMS Health listed the top 25 dispensed prescriptions in the US in 2013. Xanax and its generic, alprazolam, was the 13th most prescribed medication. Zoloft and its generic, sertraline, was the 18th most prescribed medication. Among the psychotropic medications listed they were number one and number three respectively. PsychCentral reported similar findings, with the added information that Xanax was the number one prescribed psychiatric drug in 2005, 2009, 2011 and 2013. Zoloft sank as low as the 4th most prescribed psychiatric drug in 2009 and the 3rd most in 2011.