The New York Times 8-27-22 article by Matt Richtel titled, “This Teen was prescribed 10 psychiatric drugs. She’s not alone: Increasingly, anxious and depressed teens are using multiple, and powerful psychiatric drugs, many of them untested in adolescents or for use in tandem,” provides a snapshot into the problematic “polypharmacy” to which teens and adolescents are subjected due to the horizontal, ie., non-prioritized, diagnostic system found within the DSM. 

This trend is disturbing on many levels, and is most likely only occurring because practitioners do not adhere to a traditional medical model for diagnoses discussed below. Most of these drugs are under-researched for use in teens and adolescents, the long term effects and use in tandem effects not yet known: this alone presents a problem worth avoiding.

The Richtel article focuses on the story and medication history a teen from around age 10 to 18. 

Here are the reported medicines she was prescribed:

2013: grades 4-9 on Focalin

The teen lived on the East coast, however, in my experience working in multiple states from the midwest to the West coast, this type of medication regimen is quite typical. This is an unfortunate and dangerous “standard of care.”

To begin with, one of her medications, Effexor, is not FDA approved for children or adolescents for any condition. More importantly, the risk for suicidality should be prohibitive in prescribing it. A recent article explains:

“Venlafaxine was associated with a significantly increased risk of suicidal behavior or ideation when compared with placebo…and also with five other active antidepressants (namely escitalopram (Lexapro), imipramine (Tofranil), duloxetine (Cymbalta) fluoxetine (Prozac) and paroxetine (Paxil).” 

Katherine Boaden et. al. Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment. Front. Psychiatry, 02 September 2020 Sec. Child and Adolescent Psychiatry. 

Even more recently, Cochrane researchers reported what I consider to be a curious example of understatement: “There is moderate certainty evidence that venlafaxine probably results in an “at least slightly” increased odds of suicide‐related outcomes compared with desvenlafaxine (Pristiq) and escitalopram (Lexapro).”  (Sarah E Hetrick et.al. New generation antidepressants for depression in children and adolescents: a network meta-analysis. Cochrane Database Syst Rev. 2021 May 24;5(5) )

Increased risk of mortality is supported with evidence from the American Journal of Psychiatry in 2017:

• “In our 2000–2014 data, bupropion and venlafaxine had the highest mortality indices, and they did not differ significantly. Both indices were significantly greater than that for citalopram, which in turn had a significantly higher mortality index than sertraline.
• In 2008, White et al…used a 5-year sample (2000–2004) from the National Poison Data System (NPDS) to examine serious overdose outcomes with antidepressants. Their data suggested that citalopram, venlafaxine, and bupropion were more hazardous than other second-generation antidepressants. 
• We compared our morbidity data with those reported by White et al…for the three second-generation antidepressants that those authors found most hazardous (bupropion, citalopram, and venlafaxine).
• Sertraline was included as a comparator….The mortality indices were also compared… The order from lowest to highest was the same in each data set: sertraline<citalopram<bupropion<venlafaxine.“

J. Craig Nelson, et. al. Morbidity and Mortality Associated With Medications Used in the Treatment of Depression: An Analysis of Cases Reported to U.S. Poison Control Centers, 2000–2014. Published Online:31 Jan 2017

This research is made more real in consideration of anecdotal incidences. A few years ago, a pediatrician told me that after giving a teen venlafaxine, the boy hung himself and died. These deaths are imminently avoidable, specifically by using a diagnostic model like other medical specialties.   As stated by a wise expert psychiatrist many years ago, “your treatment is only as good as your diagnosis.” 

A life and death issue for children and adolescents

Because the historic concept of Mixed Mood States dating back over a century is not taught in training programs, this issue is life or death for children and adolescents. Even though in 2013 the DSM-5 “rediscovered” this important diagnosis (which had for the most part been ignored since the DSM-I in 1952) now uses the term Mixed Features. Consequently, Mixed Mood States are poorly understood by most psychiatrists and not considered in their diagnosis for children, adolescents, or adults. 

“Mixed mood states” is generally understood as either predominant depression with subsyndromal (mild) manic symptoms, or as predominant mania with subsyndromal depressive symptoms.

 The mixed symptoms most validated by research are irritability/rage, agitation, and distractibility per Stahl et.al.; however, these are not considered by the DSM-5 because they are seen as “overlapping” with several other childhood “disorders.” According to this research, the least rated symptoms for mixed features are: elevated mood, inflated self-esteem and decreased need for sleep, i.e., classic manic symptoms. (Stahl S. et.al. CNS Spectrums (2017), 22, 203–219).

Research indicates that in up to 80% of children and adolescents, mixed states are predominant:

… children and adolescents are more likely to present with rapid cycling or to be in a mixed state [15]. Mixed states (or mixed features specifier) are a common occurrence in children and adolescents, not only in those diagnosed as having BD but also in those with a depressive episode. About 65% of a large sample with depression, either due to MDD or BD, met mixed state criteria, compared to only about 35% of children and adolescents who had only depression [16]. In one study, about 40% of adolescents with depression had BD and, of these, 82% exhibited mixed states [17], prompting the authors to conclude that mixed states were the most common presentation in this age. (bold added)

(Delfina Janiri, et.al. “Not Only Mania or Depression: Mixed States/Mixed Features in Paediatric Bipolar Disorders.” Brain Sci. March 2021, 11, 434.) 

The grab bag of medicines mentioned above for this adolescent exemplifies the diagnostic confusion built into the DSM’s horizontal diagnostic system based on symptoms which overlap with many other childhood disorders. The DSM system is additive i.e., it permits prescribers to count the required number of symptoms for any disorder and list them alongside several other disorders, justifying treating all of them at the same time, hence the “grab bag” medication regime. 

This would be the equivalent of diagnosing a “fever disorder,” a “cough disorder,” a “chest discomfort disorder,” a “tiredness disorder,” and a “sputum disorder,” in addition to Pneumonia simply because each reached a threshold count when only one diagnosis is necessary. The disease is treated first and the symptoms only for temporary relief if needed.  

Below is the psychiatric version of the vertical priority diagnostic system used in the rest of medicine:

1. Mood illnesses (mixed, manic or unipolar depression, any of which may have psychosis, agitation, distractibility, and anxiety): occupy the top position because they can explain everything below but the reverse does not. 

2. Psychotic conditions: schizophrenia & schizoaffective

3. Anxiety conditions: OCD, PTSD

4. Other: personality traits or “disorders,” ADD

                                                                             PG Surtees, RE Kendell. Br J Psych, 1979, 135:438-44

Not mentioned in the NYT article was the girl’s family history for blood relatives for any psychiatric issues, even if they were not officially diagnosed. Family history is one of the most important diagnostic validators, but is not part of the DSM criteria, which is instead based solely on symptoms for all “disorders.” The course of moods, i.e., when did they start, what are they like and their frequency, also an essential diagnostic validator, is not part of the DSM criteria for any disorder. 

The classic paper by Robins and Guze in 1970 is clearly within a traditional medical model as its lineage traced back to the 19^th century prescient ideas of Kahlbaum and Kraepelin of course and outcome, the most important of the diagnostic validators in psychiatry. (Robins E. Guze S. Establishment of Diagnostic Validity in Psychiatric Illness: Its application to Schizophrenia. AJP, Vol. 126, issue 7, January 1970 pp. 983-987).

1. Course – of primary importance
2. Symptoms – needed
3. Genetics (family history) – of primary importance
4. Treatment effects (least specific)
5. Lab tests or diagnostic markers – (nothing yet accepted by mainstream psychiatry in the past 40 years except for Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] test) and a treponemal test) when neurosyphilis was known to cause psychosis, mania and depression since the late 1940’s and could be cured with penicillin in the early stages). 

Only symptoms are part of the DSM diagnostic criteria for any disorder since DSM-I 1952. 

The current standard of care for adults and children is to first diagnose Major Depressive Disorder (MDD) as according to the DSM, without asking about subsyndromal symptoms (i.e. mild manic symptoms); and second, to prescribe an antidepressant. If the mild manic symptoms are discovered in the initial evaluations, neither antidepressants or stimulants are recommended and the child/adolescent should be started on a low dose dopamine blocker like lurasidone (Latuda) or asenapine (Saphris), which are both FDA approved for 10 and over. Furthermore, their use is supported by research for mixed mood states. Abilify could also be used. The medicine treatment should re-evaluated after 3-4 months. 

In adults with Mixed Mood States, several medications would be appropriate: cariprazine (Vraylar) is FDA approved for mixed states; lurasidone (Latuda) is not FDA approved, but has good research for mixed moods and asenapine (Saphris), FDA approved for acute mania/mixed mania as an adjunct to lithium or valproate for adults; Ziprasidone (Geodon) also has research for mixed mood states but no FDA approval. 

The majority of practicing psychiatrists are not trained to ask about the mild, i.e., subsyndromal manic symptoms. Why this is essential is explained in the 2007 2^nd edition of Manic-Depressive Illness – Bipolar Disorder and Recurrent Depression: 

• “The patient’s self-report is not sufficient for a dependable denial of past hypomanic or manic episodes, due to the problem of lack of insight, considering any mood that is not depressed as normal.

• Also, patients are often in such psychic pain during a depressive episode that they can be unmotivated to search their memory carefully for times when they may have felt better (albeit pathologically). 

• It is strongly recommended by many experts that before a patient be given a diagnosis of “MDD,” i.e., pure unipolar depression, a close family member or spouse needs to be contacted to elicit subsyndromal or syndromal hypomanic or manic and/or mixed symptoms, if any before prescribing antidepressants.

• False unipolar depression, sometimes called pseudo-unipolar depression characterized by non-euphoric psychomotor agitation, irritability and distractibility, i.e. mixed states, occurs in at least 50% of supposed MDD (higher on inpatient) since it is well known that patients rarely volunteer these symptoms but will call themselves “depressed” because they feel unhappy.  Relatives however do report these symptoms as well as subsyndromal hypomanic symptoms.”

Low dose mood stabilizers like lithium 300-600 mg per day or valproate (Depakote) 500 mg, in conjunction with a dopamine blocker mentioned above, can also be used. 

The girl in the NYT article is a sad, but not uncommon, example of the broken mindset of a diagnostic system embedded within the DSM. Children and adults should not have to take up to 10 medicines or risk death due to this misguided diagnostic process and its subsequent treatments.