Therapeutic trial can diagnose ADHD

THE comment by Professor Jon Jureidini in MJA InSight entitled Think twice before prescribing for ADHD is both timely and important. It raises basic issues about the diagnosis (and therefore the management) of attention deficit hyperactivity disorder (ADHD) and other conditions listed and described in the fifth edition of the Diagnostic and statistical manual of mental disorders (DSM-5). 

Our knowledge of the underlying pathology, pathophysiology and aetiology of these problems is much less than for physical diseases. Until we have this deeper knowledge, our diagnoses and management will be inexact.

In the past 200 years, physical medicine has passed from the symptoms and syndromes to diagnoses based on pathology and aetiology, giving better management and outcomes.

Psychiatric and behavioural medicine started down this pathway much later.

It is now accepted that most psychiatric and behavioural conditions are associated with changes in the brain, but in spite of extensive research, most behavioural disorders are still syndromes.

The DSM-IV and DSM-5 diagnoses are based on collections of signs and symptoms, with no reference to the underlying pathology or aetiology.

• Related: MJA InSight — Think twice before prescribing for ADHD
• Related: MJA — ADHD and psychostimulants — overdiagnosis and overprescription
• Related: MJA InSight — ADHD meds + party drugs “complex cocktail”
• Related: MJA — ADHD medication overdose and misuse: the NSW Poisons Information Centre experience, 2004–2014

The DSM-5 diagnosis of ADHD should be called “ADH syndrome” to recognise that this collection of symptoms and signs may arise from various social, environmental and physical pathologies. We still lack insight into the aetiological causes and pathological changes.

Once we accept that ADHD (and other behavioural disorders classified by the DSM-5) is not a single disease with a single cause and pathology, but rather a syndrome with different aetiologies and pathologies, then the diagnosis and management will become more rational and logical. Examples of potential underlying causes of ADH syndrome include:

1. Fetal alcohol spectrum disorder (FASD). Many of these children have microcephaly, delayed learning ability and about 63% also meet the DSM-IV and DSM-5 criteria for ADHD.
2. Down syndrome. About 44% of children with Down syndrome have behavioural patterns that meet the DSM-5 criteria for ADHD. 
3. Developmental delay. Some children with delayed cognitive development meet the DSM-5 criteria for ADHD. A 5-year-old delayed child may have the behaviour of a normal 3-year-old child, with its lack of control and responsibility, short attention span and uninhibited activity.
4. Low socio-economic status. Most practicing paediatricians have seen large families of noisy, ill-disciplined, irresponsible and hyperactive children who often fit the ADH syndrome. Often these families have a single parent (usually the mother), many subsist on support payments, move frequently from town to town and all the children have poor levels of school attendance, behaviour and performance.
5. Failure to reach potential. We have also seen children, usually only one child in an otherwise controlled, aspiring family, who appears to be mentally bright but cannot settle at school, annoys his or her parents and siblings and, if sufficiently pathological, can destroy a family. 

These groups have different aetiologies and may also have different pathologies. They also respond differently to behavioural, cognitive and drug therapies.

Professor Jureidini’s suggestions for identifying these groups are essential, but not always accurate. Based on those criteria, together with some testing to support our clinical opinions, we can put most children with ADH syndrome into one of these groups.

Biochemical ADHD, which I call “ADH disease”, commonly involves abnormalities in the dopamine or serotonin pathways in the basal brain nuclei or the pre-frontal cortex.

These pathways are often impaired in brain damage (as in FASD) and also by specific (often genetic) changes as in the child in group 5. 

However, these five groups are not necessarily definite or mutually exclusive.

Children with ADH disease respond very well to drugs that activate this pathway, such as methylphenidate (Ritalin), dexamphetamine and other related drugs.

If I suspect ADH disease, and also if a parent demands treatment (“give him the tablets, Doc”), I have a standard 2-week trial with methylphenidate. It is given in the mornings in increasing doses up to 20 mg.

If the parents and the class teacher say that there is a dramatic improvement with the appropriate dose, the effect wears off after about 4–6 hours and, when the trial is finished, the child reverts to his old self, then, and only then, I will give longer term medication.

Other medications could be tested in the same way. This management is empirical, but it works, and as I gather data, I can associate success with specific items in the DSM-5 criteria and increase the sensitivity and specificity of these markers.

Thirty years ago there were many patients with chronic diarrhoea of unknown cause – the chronic diarrhoea syndrome. Coeliac disease was isolated by a therapeutic trial of gluten avoidance. The patient improved when gluten was stopped and relapsed when it was restarted. We now make the diagnosis with blood tests.

We can now diagnose ADH disease by a therapeutic trial. We look forward to specific diagnostic tests as we now have for coeliac disease.

Alan Dugdale is honorary professor of paediatrics and child health at the University of Queensland and honorary professor of paediatrics at Griffith University.