Successful Treatment of Insomnia with Melatonin in a Patient with Malignant Glioma after Radiotherapy-Involving the Pineal Gland

A 29 year old female patient suffering from a biopsy proven anaplastic astrocytoma in the right basal ganglia was treated by conformal radiation therapy with 2 Gy/fraction up to 60 Gy. Near the end of radiotherapy she complained about insomnia. Her previous sleep pattern has been inconspicuous, but now – despite high dose of benzodiazepines provided by her family physician she was unable to fall asleep until 2 am and to stay asleep for longer than two hours. Following the hypothesis that melatonin secretion had been impaired by radiotherapy, the patient was given 3 mg of melatonin orally at bedtime with immediate and ongoing restauration of sleep pattern.


Introduction
A recent survey reported on conspicuous prevalence and severity of sleep disorders in patients with cancer.Insomnia is defined as difficulty falling asleep, difficulty staying asleep -with wake episodes of more than half an hour -unintended early awakening and nonrestorative sleep.This symptom complex qualifies as insomnia when it occurs at least three times a week, results in distress and impairs day time functioning.In cancer patients, especially in patients complaining about fatigue and insomnia is under diagnosed and undertreated [1][2][3][4][5][6][7].
Insomnia is also very common in patients with malignant gliomas, although not frequently as striking as in the patient reported here [8].
2 underwent conformal radiotherapy with 2 Gy single doses up to 60 Gy.Because of headaches three weeks after the start of radiation, she was treated with dexamethasone up to 12 mg daily.
Two weeks later, she reported that her headache was gone, but that she was continuously active day and night, felt restlessly "driven from outside".Going to bed around 10 pm ordinarily she was now unable to fall asleep before 2 am and woke up 1.5 to 2 hours later.Because of sleep deprivation, her family physician prescribed nitrazepam 5 mg taken at bedtime.Despite an increase of the nitrapazepam (dose of up to 4 tablets) her sleep lasted no longer than two hours.
A capsule with 3 mg of melatonin taken at 10 pm allowed her to fall asleep again and to stay asleep for five to six hours from the first day of administration of melatonin, even without benzodiazepine medication on subsequent days.She had regenerative sleep again and felt active at day time.

Discussion
The hormone melatonin (N-acetyl-5-methoxytryptamine) is secreted in the pineal gland during darkness or when the absorption of blue light (484 nm) is blocked.Melatonin is an important factor of the sleep-wake cycle, mainly regulated by the suprachiasmatic nuclei of the hypothalamus [9,10].In the US, melatonin is widely used as over the counter medicine against sleep disorders, jet lag and various other conditions as it is a powerful antioxidant, whereas in Europe, its medical use focuses on insomnia in persons above the age of 55 years.However, with rare exceptions, melatonin is well tolerated in doses below 5 mg [11][12][13][14][15] and potential anti-tumoral effectiveness of melatonin has been discussed [16].
The patient mentioned in this report showed multiple causes for disturbed sleep, starting from reactive depression over an incurable tumor disease, increased stress about this illness and its sequelae for her personal situation and the family, disruption of sleeping pattern due to the anti-edematous medication with dexamethasone [17][18][19][20][21][22] and a possible hypomanic state due to this same medication [23].
In the patient of this report, the radiation field covered the epiphysis as well as both hypothalamic suprachiasmatic nuclei, where the circadian rhythms of waking and sleep are regulated (Figure 2 and Table 1).Trying melatonin therapy was obvious -and successful.Thus, in patients with radiation fields covering the hypothalamus or the epiphysis with insomnia, the administration of melatonin may offer restoration of satisfactory sleep patterns.

Table 1 :
Minimal, maximal, median and average doses of the risk organs and CTV (clinical target volume), PTV (planning target volume).