Early psychiatric diagnosis is rare, but possible, and kind

Early psychiatric diagnosis is all too rare, but it’s possible, and it’s kind

Many disorders begin early in life, and early psychiatric diagnosis is possible [1]

Early psychiatric diagnosis is all too rare

Median delays among cases eventually making contact ranged from 3.0 to 30.0 years for anxiety disorders, from 1.0 to 14.0 years for mood disorders, and from 6.0 to 18.0 years for substance use disorders.

…early-onset disorders were associated with lower probabilities of initial treatment contact in most countries. One explanation for this finding may be that minors need the help of parents or other adults to seek treatment, and recognition is often low among these adults unless symptoms are severe… In addition, child and adolescent- onset mental disorders may be associated with normalization of symptoms or development of coping strategies (e.g., social withdrawal in social phobias) that interfere with help-seeking later in life.

…our earlier analyses of the U.S. data revealed that even those with severe and impairing disorders have substantial delays in initial treatment contact…[2]

Young people are less likely to seek help if they:

  • are experiencing suicidal thoughts and depressive symptoms;
  • hold negative attitudes toward seeking help or have had negative past experiences with sources of help; or
  • hold beliefs that they should be able to sort out their own mental health problems on their own.[3]

Early psychiatric diagnosis is possible

Initial treatment contacts appear to be fastest for mood disorders, perhaps because these disorders have been targeted in some countries by educational campaigns, primary care quality improvement programs, and treatment advances… On the other hand, the longer delays for anxiety disorders may be due to the earlier age of onset of some conditions (e.g., phobias), fewer associated impairments, and even fear of providers or treatments involving social interactions (e.g., talking therapies, group settings, waiting rooms)…

Women have been shown in prior research to be faster than men at translating nonspecific feelings of distress into conscious recognition that they have emotional problems, perhaps explaining the significantly higher rates of initial treatment contact by women in some countries…

More recent cohorts were also significantly more likely to make eventual treatment contact, perhaps suggesting a positive outcome of programs recently attempted in some countries to destigmatize and increase awareness of mental illness, of screening and outreach initiatives, of the introduction and direct-to-consumer promotion of new treatments, and of expansion of insurance programs…[2]

Young people are more inclined to seek help for mental health problems if they:

  • have some knowledge about mental health issues and sources of help;
  • feel emotionally competent to express their feelings; and
  • have established and trusted relationships with potential help providers.[3]

Early psychiatric diagnosis is kind

Lifetime Prevalence of Disorders

Any anxiety disorder
Any mood disorder
Any impulse-control disorder
Any substance use disorder
Any disorder


Depression is a major human blight. Globally, it is responsible for more ‘years lost’ to disability than any other condition. This is largely because so many people suffer from it — some 350 million, according to the World Health Organization — and the fact that it lasts for many years. (When ranked by disability and death combined, depression comes ninth behind prolific killers such as heart disease, stroke and HIV.) [5]

…preclinical, epidemiologic, and trial data… suggest that even milder disorders, if left untreated, lead to greater severity, additional psychiatric comorbidity, and negative social and occupational functioning…[2]

  1. Merikangas, Kathleen Ries, et al. “Lifetime prevalence of mental disorders in US adolescents: results from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A).” Journal of the American Academy of Child & Adolescent Psychiatry 49.10 (2010): 980-989.
  2. Wang, P. S., et al. “Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization’s World Mental Health Survey Initiative.” World psychiatry: official journal of the World Psychiatric Association (WPA) 6.3 (2007): 177-185.
  3. Rickwood, Debra J., Frank P. Deane, and Coralie J. Wilson. “When and how do young people seek professional help for mental health problems.” Med J Aust 187.7 Suppl (2007): S35-S39.
  4. Kessler, Ronald C., et al. “Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.” Archives of general psychiatry 62.6 (2005): 593-602.
  5. Smith, Kerri. “Mental health: a world of depression.” Nature 515.7526 (2014): 181.

Psychiatric medication development restrained by insurance regulation and FDA

Restraint of patient in stretcher illustrates restraint of psychiatric medication development by insurance regulation and FDA

Psychiatric medication development declined steeply after the 1950s and 1960s

…there has been a steep decline in the development of new medication classes. Instead of new molecular entities, slight molecular modifications producing ‘‘me-too’’ drugs attempted to garner market share.

The current deficit in novel agents contrasts sharply with the 1950s. Then, there was a sudden efflorescence of potent psychiatric therapeutic agents. The pace of discovery of entirely new classes of psychotropic drugs was dizzying. These included lithium, lysergic acid diethylamide (LSD), chlorpromazine, iproniazid, reserpine, imipramine, chlordiazepoxide, haloperidol, and clozapine.

These discoveries resulted from chance observations of unexpected clinical benefits rather than being derived from basic neuroscience. All major classes were serendipitously discovered by 1969. For instance, chlorpromazine was a pre-surgical antihistamine sedative whose antipsychotic properties were completely unsuspected. Imipramine was developed as a chlorpromazine ‘‘me-too,’’ but turned out to be an antidepressant. Conversely, clozapine was a potential antidepressant, but turned out to be an antipsychotic with remarkably low extrapyramidal toxicity and superior efficacy.

What stymied generative serendipity over the next 40 years? A number of elements came together.

  • The most important factor may have been the drastic change in medical practice economics. Hospital-based academic research was supported from clinical income. That freed up clinicians for therapeutic explorations. However, ‘‘managed care’’ declared this irrelevant to patient care and markedly shortened hospital stays.
  • Second, often patients were discharged before the effects of a new therapeutic regimen became clear.
  • Third, industry became concerned with immediate return on their investments, which were limited by extensive regulations, liability concerns, and exhaustive preclinical animal model testing.
  • Fourth, the growth of clinical research organizations (CROs) diverted industrial support from investigator-initiated academic research to relatively inexpensive, pre-set industrial protocols.

Psychiatric medication development trials could be much better for patients both in trials and in treatment

The standard randomized parallel-group design leaves a crucial causal ambiguity. If 60% of those treated with medication have substantial improvements, while only 30% of those on placebo improve (assuming statistical significance), then in about half of those who seemed to have a direct drug benefit, the drug was actually not required. Identifying individuals who actually require medication to improve and maintain their gains remains obscure. Therefore, attempts to determine how a drug brought about its benefits by studying those who improved during drug treatment are handicapped by study of a causally heterogeneous mixture.

…an alternative design would be to initially and openly treat all patients with the putative medication, titrating for the individual’s optimal dose, until it is clear if the patient was not a treatment responder. These subjects would leave the trial. Apparent responders would be maintained on medication for a period, but then randomly, and in double-blind fashion, switched to placebo or remain on medication. All patients would be followed independently and closely, blind to treatment status, for defined signs of worsening. At a predetermined level of modest worsening, double-blind medication retreatment would start. A worsening rate higher in the placebo-substituted group than in the medication-maintained group would provide clear evidence of medication efficacy. Those individuals who worsened on slow placebo substitution and then improved on medication re-treatment are very likely specific drug responders. Those who switched to placebo and nevertheless continued to do well would be far less likely to be specific medication responders.

To summarize, this design would determine individuals very likely to be medication-specific responders, very likely non-specific responders, and non-responders.

Other practical benefits are that all patients initially receive active treatment. This fosters recruitment, since many patients will not risk being initially assigned to placebo. In addition, patients will learn if medication is necessary for them to remit or that they have sufficient resources.

In fact, academic investigators have successfully used this design.

  1. Weingart, Scott. “Podcast 060 – On Human Bondage and the Art of the Chemical Takedown.” org, 13 Nov. 2011, emcrit.org/podcasts/human-bondage-chemical-takedown/. Accessed 25 Feb. 2017.
  2. Klein, Donald F., and Ira D. Glick. “Industry withdrawal from psychiatric medication development.” Revista Brasileira de Psiquiatria 36.3 (2014): 259-261.

Psychiatry on East Coast and West Coast lagged behind Midwest

Lying on psychiatry couch, patient reads that doctor's diploma is from Institute of Professional Help.

…by 1960 psychoanalytically oriented psychiatry had become the prevailing model for understanding all mental and some physical illnesses.

…the whole thrust of psychoanalytic psychiatry at the Massachusetts Mental Health Center, and perhaps at Harvard Medical School in general, was not simply to develop better psychiatrists but to develop better therapists—therapists prepared to understand and empathize with the patients’ existential problems.

…a lack of critical questioning seemed to be widespread in Boston and at many other institutions on the east and west coasts of the country.  There were… no grand rounds at the Massachusetts Mental Health Center. No outside speakers were invited to address the house officers on a regular basis to discuss current clinical or scientific issues.

…in 1965… several of us tried to recruit a psychiatrist in the Boston area to speak about the genetic basis of mental illness. We could find no one; not a single psychiatrist in all of Boston was concerned with or even had thought seriously about that issue…

…new and effective treatments, in the form of psychopharmacological drugs, began to be available. Initially, a number of supervisors discouraged us from using them, believing that they were designed more to aid our anxiety than that of the patients.

…scholarly concerns were not lacking at Washington University under Eli Robins, at a number of other centers in the Midwest, or at Johns Hopkins University under Seymour Kety…

By the mid-1970s… psychiatry… had effective treatments for the major mental illnesses and something that began to approach a practical cure for two of the three most devastating diseases: depression and manic-depressive illness.

…led first by Eli Robins at Washington University and then by Robert Spitzer at Columbia University’s New York State Psychiatric Institute, new clinically validated and objective criteria were established for diagnosing mental illness.

…Seymour Kety used his leadership position at NIH to spark a renewed interest in the biology of mental illness and specifically in the genetics of schizophrenia and depression.[2]

  1. Stevens, Mick. “man lying on psychiatrist’s couch looks up at diploma on wall: ‘Institute… – Cartoon.” CondeNastStore, www.condenaststore.com/-sp/man-lying-on-psychiatrist-s-couch-looks-up-at-diploma-on-wall-Institute-Cartoon-Prints_i8640495_.htm. Accessed on 12 Nov. 2016.
  2. Kandel, Eric R. “Biology and the future of psychoanalysis: a new intellectual framework for psychiatry revisited.” American journal of Psychiatry 156.4 (1999): 505-524.