Kindling

What is Kindling?

In psychopharmacology, “kindling” refers to a process in which repeated episodes of withdrawal - such as successive cycles of stopping and restarting a medication - may lead to progressively greater nervous-system sensitisation and increasingly severe withdrawal responses over time.¹ While classically associated with alcohol²  ³ and benzodiazepines⁴, the concept of kindling or sensitisation has also been proposed in relation to non-benzodiazepine antidepressant treatment and repeated antidepressant withdrawal, and is increasingly discussed within patient communities in relation to severe or protracted discontinuation symptoms.¹

NICE identifies a history of previous withdrawal symptoms as a factor clinicians should consider when assessing someone's risk of problems during a future withdrawal.⁵

Signs of Kindling 

There is no diagnostic test for psychiatric-drug kindling, nor is there a universally accepted set of diagnostic criteria. Within withdrawal communities, the term is commonly used when someone notices patterns such as:

• previously tolerated dose reductions becoming increasingly difficult

• increasingly intense reactions following medication changes

• pronounced symptoms following missed doses

• difficulty tolerating changes that previously caused little difficulty

• worsening following repeated stop-start withdrawal attempts

• heightened sensitivity following abrupt cessation and subsequent reinstatement

• withdrawal symptoms appearing after progressively smaller reductions.

[See also: Acute Withdrawal | Protracted Withdrawal | Interdose Withdrawal]

The Stop–Start Cycle

One of the situations in which the concept of kindling becomes particularly relevant is repeated withdrawal and reinstatement. A patient may stop a medication rapidly and develop severe withdrawal. The medication is then restarted, symptoms settle to some degree, and another attempt is then made to stop. If this process happens repeatedly, patients sometimes report that each attempt becomes more difficult, with worsening withdrawal symptoms and potential for paradoxical reactions.

This does not mean that reinstatement itself inevitably causes kindling, nor that somebody who has previously stopped a medication can never safely attempt withdrawal again. Rather, previous difficulty withdrawing is information that should influence how cautiously another attempt is approached.

The Danger of 'Just Pushing Through'

When withdrawal symptoms become severe after a reduction, continuing to make scheduled reductions regardless of the person's response can make withdrawal unnecessarily difficult and potentially dangerous. A taper should not become a rigid timetable that the patient is expected to endure at all costs.

NICE recommends that withdrawal schedules remain flexible. If distressing symptoms develop following a reduction, options include delaying the next reduction, making a smaller reduction, or returning to the previous dose, depending on the individual clinical circumstances. Subsequent reductions should be adjusted according to the person's response.⁵

This is particularly important for someone with a history of difficult withdrawal.

Reducing the Risk of Repeated Destabilisation

There is no proven intervention that can guarantee prevention of kindling. However, established withdrawal guidance provides several principles that may reduce unnecessary withdrawal stress:

1. Avoid abrupt cessation where possible. Benzodiazepines, Z-drugs, opioids and antidepressants should generally be withdrawn gradually rather than stopped suddenly.⁵

2. Allow symptoms to guide the taper. A reduction schedule should be modified if withdrawal symptoms become intolerable, rather than continuing reductions simply because a predetermined date has arrived.⁵

3. Use progressively smaller reductions where appropriate. For antidepressants, benzodiazepines, Z-drugs and opioids, NICE recommends a slow, stepwise reduction proportionate to the existing dose, so that reductions become smaller as the dose becomes lower.⁵ Pharmharmed.ie endorses the gold-standard hyperbolic tapering method outlined by Horowitz & Taylor's Maudsley Deprescribing Guidelines. 

4. Take previous withdrawal seriously. Someone who experienced significant withdrawal during a previous attempt may require a substantially more cautious approach during another attempt. NICE specifically recognises previous withdrawal symptoms as a relevant risk factor.⁵

[See: Hyperbolic Tapering]

References

1. Fava, G. A. (2020). The mechanisms of tolerance and withdrawal: Implications for antidepressant discontinuation. Psychotherapy and Psychosomatics, 89(3), 129–138. https://doi.org/10.1159/000506868

2. Stephens, D. N., Ripley, T. L., Borlikova, G., Schubert, M., Albrecht, D., Hogarth, L., & Duka, T. (2005). Repeated ethanol exposure and withdrawal and the kindling concept: Evidence for persistent changes in CNS function. Alcoholism: Clinical and Experimental Research, 29(9), 1724–1730.) 

3. Becker, H. C. (1998). Kindling in alcohol withdrawal. Alcohol Health & Research World, 22(1), 25–33.) 

4. Ward, B. O., & Stephens, D. N. (1998). Sensitisation of withdrawal signs following repeated withdrawal from a benzodiazepine: Differences between measures of anxiety and seizure sensitivity. Psychopharmacology, 135(4), 342–352. https://doi.org/10.1007/s002130050521

5. (National Institute for Health and Care Excellence. (2022). Medicines associated with dependence or withdrawal symptoms: Safe prescribing and withdrawal management for adults (NG215). https://www.nice.org.uk/guidance/ng215