Dexamethasone for ADHD

• 1. Suggestion of dexamethasone shock treatment for ADHD-HI
• 2. Differentiation from long-term 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 reaction in order to shut down the HPA axis properly.

Irrespective of this, a significant number of ADHD-HI sufferers also have an excess of (cortisol-affine) mineralocorticoid receptors (MR) or a desensitization of the glucocorticoid receptors (GR), which is why, in the absence of sufficient GR activation, switching off the HPA axis is not successful even with a high cortisol stress response or dexamethasone administration.

This only applies to ADHD-HI. In ADHD-I (without hyperactivity), reduced GR activity is rare, so that the increased cortisol stress response there ensures sufficient HPA axis resetting. The dexamethasone shock treatment considered here is therefore only suitable for ADHD-HI sufferers and not for ADHD-I sufferers. Moreover, in ADHD-HI sufferers, it can only work in those who show sufficient cortisol suppression by dexamethasone. This is more likely in ADHD-HI sufferers with lower levels of hyperactivity, so dexamethasone shock treatment may tend to work more for ADHD-HI sufferers with a less severe symptom picture.

As a result, nonsuppression of the HPA axis is likely to occur more frequently in ADHD-HI, but is not always present.

More about tests to diagnose ADHD using the dexamethasone test (DST) at ⇒ Endocrine function tests for ADHD In the chapter ⇒ Pharmacological endocrine function tests.

From a scientific point of view, we suggest the following approach as a treatment option for ADHD-HI sufferers:

1. A DST is performed to determine whether suppression occurs.
Only in this case is dexamethasone shock treatment theoretically even an option.
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 the case of a general adrenal insufficiency (e.g. due to insufficient ACTH secretion, which could be triggered by downregulation of the CRH receptors of the pituitary gland), measuring the CRH values could help. However, a CRH deficiency is also conceivable, as can be triggered by prolonged cortisol administration, for example.¹

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

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

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

This proposal is purely scientific and has so far been based solely on theoretical considerations. It has not yet been tested in practice.
Isolated treatment with dexamethasone should have no greater risks than carrying out dexamethasone tests. Theoretically, the administration of dexamethasone should only replace the amount of cortisol that is released during a healthy stress response of the HPA axis and that causes the HPA axis to shut down again in a healthy state.
While long-term low-dose cortisol administration, as is common in the treatment of inflammatory problems, can lead to downregulation of the corticoid receptors and a reduction in cortisol production by the adrenal cortex, this risk is significantly lower with infrequent shock treatment.
We do not know at what frequency of treatment with dexamethasone risks could arise 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 with cortisol / dexamethasone? In the article ⇒ Cortisol and other stress hormones in ADHD.

2. Differentiation from long-term 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 (within 4 days) leads to negative moods such as anger and sadness.³