Dexamethasone for ADHD

• 1. Suggestion of dexamethasone shock treatment for ADHD-HI
• 2. Differentiation from continuous treatment with dexamethasone

1. Suggestion of dexamethasone shock treatment for ADHD-HI¶

In many ADHD-HI sufferers (with hyperactivity), the cortisol stress response is flattened. We suspect that this leads to too little cortisol being released at the end of a severe stress response to cleanly shut down the HPA axis again.

Regardless, in a substantial number of ADHD-HI sufferers, there is additionally an exaggeration of the (more cortisol affine) mineralocorticoid receptors (MR) or a desensitization of the glucocorticoid receptors (GR), which is why, in the absence of sufficient GR activation, a shutdown of the HPA axis is not successful even by a high cortisol stress response or dexamethasone administration.

This exclusively concerns ADHD-HI. In ADHD-I (without hyperactivity), decreased GR activity is rare, so that sufficient HPA-axis reswitching is given by the increased cortisol stress response there. Therefore, the dexamethasone shock treatment considered here is only suitable for ADHD-HI and not ADHD-I sufferers. Moreover, in ADHD-HI sufferers, it can work only in those who show sufficient cortisol suppression by dexamethasone. This is more likely in ADHD-HI sufferers with lower hyperactivity expression, so dexamethasone shock treatment might tend to work more for ADHD-HI sufferers with a less severe symptom picture.

In conclusion, HPA axis nonsuppression is likely to be more common in ADHD-HI, but not always present.

For more on studies to diagnose ADHD using the dexamethasone test (DST), see ⇒ Endocrine function tests in ADHD In the chapter ⇒ Pharmacologic endocrine function tests.

As a treatment option for ADHD-HI sufferers, we propose the following approach from a scientific perspective:

1. A DST is performed to determine if suppression occurs.
Only in this case dexamethasone shock treatment can theoretically be considered at all.
If suppression occurs, the DST result shows how low the individual cortisol level is in the resting state of the HPA axis.

2. Measurements of the cortisol level every 1 to 3 days (important: always at the same time of day) can determine whether the cortisol level increases again. This would be a sign of activation of the HPA axis.
In case of a general adrenal insufficiency (e.g. due to too low ACTH secretion, which could be triggered by a downregulation of the CRH receptors of the pituitary gland), a measurement of CRH levels could help. However, a deficiency of CRH is also conceivable, as it can be triggered, for example, by prolonged cortisol administration.¹

3. If a cortisol level increase is detected, a measurement on the following day could check whether the cortisol level also decreases again. This would be an indication of a functioning autonomic regulation of the HPA axis reswitching. In this case, no treatment would be necessary.

4. However, if the cortisol level remains elevated for several days compared to the cortisol level measured initially after dexamethasone administration, the HPA axis could be stimulated to suppression again by a single dose of dexamethasone (at the dosage that was successful in DST).

5. Follow-up measurements (initially daily) can monitor at what frequency the HPA axis is activated and remains stuck at this elevated level.

This proposal is made from a purely scientific point of view and is so far based solely on theoretical considerations. It has not yet been tested in practice.
Sporadic treatment with dexamethasone should have no greater risks than dexamethasone testing. Dexamethasone administration should theoretically only replace the amount of cortisol secreted during a healthy stress response of the HPA axis, which causes the HPA axis to shut down again in a healthy state.
While prolonged low-dose cortisol administration, as is common in the treatment of inflammatory problems, can lead to downregulation of corticoid receptors and a reduction in cortisol production by the adrenal cortex, this risk is much lower with infrequent shock treatment.
At what frequency of treatment with dexamethasone risks might arise is not known to us and must be considered with appropriate medical caution.
As always, the risks must be weighed against the benefits for those affected.

More on dexamethasone for ADHD at ⇒ Treatment of ADHD by cortisol / dexamethasone? In the article ⇒ Cortisol and other stress hormones in ADHD.

2. Differentiation from continuous treatment with dexamethasone¶

While short-term administration of dexamethasone (as well as short-term administration of cortisol) increases activation and concentration and reduces fatigue, prolonged administration of dexamethasone (as early as within 4 days) leads to negative mood such as anger and sadness.³