Academic journal article South African Journal of Psychiatry

Alternative Psychosis (Forced Normalisation) in Epilepsy

Academic journal article South African Journal of Psychiatry

Alternative Psychosis (Forced Normalisation) in Epilepsy

Article excerpt

Brief episodes of abnormal behaviour have been recorded after dramatic reduction of seizures using anti-epileptic drugs (AEDs). This phenomenon is called alternative psychosis, or forced normalisation when supportive electro-encephalogram (EEG) evidence is available. (1-5)

Landolt was the first to report improvement in EEG activity during periods of abnormal behaviour. (6-9) The mechanism of forced normalisation is still not fully understood, although the kindling phenomenon, the phenomenon of long-term potentiation and the channel disorder paradigm have all been proposed as possible explanations. (10,11) Another theory relating to this phenomenon states that epileptiform discharges may mimic electroconvulsive therapy in a focal area and this seizure suppression may lead to psychopathology. (2)

Patients with refractory temporal lobe epilepsy who undergo unilateral anterior temporal lobectomy have been observed to develop a de novo psychosis with diminished seizures.

This is thought to be an alternative psychosis related to forced normalisation of the EEG. (8,12-14)

The absence of clear diagnostic criteria for forced normalisation has been an impediment both to its routine diagnosis and to further research. Research into this phenomenon has been confined mainly to case reports (as in this case) or to retrospective studies. (6)

Anticonvulsant drugs have been associated with new-onset depression and psychosis. If anticonvulsants have recently been changed, this should always be considered as a potential cause of a new or worsening depressive or psychotic illness. (15,16)

There are case reports in the literature describing psychosis relating to topiramate, zonisamide and levetracetam (see Table I for a list of drugs implicated in forced normalisation). Some of these reports may relate to the process of forced normalisation, in which a diminished frequency of seizures allows psychotic symptoms to emerge. (15,17)

Krishnamoorthy and Trimble list questions posed by other researchers that still remain unanswered: (6)

1. Should the EEG necessarily be completely normal for this diagnosis to be made, or should relative normalisation also be included?

2. What is the relationship of the EEG to suppression of seizures?

3. I s alternative psychosis the expression of forced normalisation, a variant, or unrelated to it?

The current approach is wider inclusion of cases that show a decrease in seizure frequency with both relative and complete normalisation of the EEG.

The following are the proposed criteria for forced normalisation: (6)

Primary (essential) criteria:

1. Established diagnosis of epilepsy based on clinical history, EEG and imaging

2. Presence of a behavioural disturbance of acute/sub-acute onset characterised by one of the following :

* psychosis with thought disorder, delusions, hallucinations

* significant mood change, mania/hypomania or depression

* anxiety with depersonalisation, derealisation

* hysteria: motor, sensory, abasia

3A. Reduction in the total number of spikes counted in a 60-minute awake EEG recording with a normal 16-channel machine, using standard 10-20 electrode placement, by over 50% compared with a similar recording performed during a normal state of behaviour


3B. Report of complete cessation of seizures for at least 1 week, corroborated by a relative or a carer.

Supportive criteria:

1. Recent change (within 30 days) of pharmaco-therapeutic regimen

2. Report of similar episodes of seizure cessation and behavioural disturbance in the past, from close relative, carer or general practitioner, or documentation of these in hospital records, with or without EEG evidence. This may or may not be linked with anticonvulsant drugs.

The diagnosis is made in the presence of:

Primary criteria 1, 2 and 3A


Primary criteria 1, 2 and 3B and one supportive criterion. …

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