Baclofen

Observational studies

In a trial of baclofen in suppressing alcohol consumption in 148 alcohol-dependent subjects with alcoholic liver cirrhosis it was well tolerated [ ].

Cardiovascular

Extreme bradycardia and hypotension has been reported in a tetraplegic patient given oral baclofen [ ]. Another dose resulted in the same complications. However, this patient had a history of autonomic dysreflexia.

Nervous system ( See also Drug withdrawal )

Altered consciousness is a major adverse effect of baclofen, because of its GABA-mimetic effects. While this reflects global nervous system depression, other adverse effects, such as seizures and dyskinesias, are probably better explained by selective effects on different brain areas. A case of akinetic mutism associated with baclofen might be an example of this [ ].

• A 76-year-old man with a history of cognitive decline of unknown origin had severe contractures with increasing pain in his legs. He was given baclofen 10 mg tds, and 2 days later had difficulty following commands. Another 2 days later he could not speak and would not follow commands, although he was alert with his eyes open. He had no spontaneous movements, but would withdraw to painful stimuli. The electroencephalogram showed intermittent, bilateral, symmetrical, sharp waves. Computed tomography and laboratory tests showed no specific abnormalities. Baclofen was withdrawn and he improved over the next 4 days, after which there was no difference to his pre-baclofen condition.

The authors explained that akinetic mutism occurs when bilateral frontal lobe or diencephalic–mesencephalic dysfunction interrupts the limbic circuitry. As symptoms were observed immediately after the start of treatment and resolved completely after withdrawal, the condition was probably caused by baclofen. It is not known why baclofen in this case impaired neuronal activity specifically in these areas. The authors found only one previous report describing the case of a 57-year-old woman with end-stage renal insufficiency, who developed akinetic mutism after a single dose of baclofen [ ]. In this case, the symptoms resolved after dialysis. Therefore, adverse effects of baclofen should be suspected if neuropsychiatric symptoms occur after baclofen treatment has been started. Electroencephalography and computerized tomography may be necessary to exclude other causes.

Because the systemic effects of baclofen can cause a reduced level of consciousness, intrathecal administration via a catheter is widely used to avoid systemic effects. However, because a continuous infusion is required, implantable pumps containing a very concentrated solution of baclofen are used to avoid frequent refills. Inadvertent subarachnoid bolus administration of a concentrated solution will produce cranial spread of baclofen within the CSF, resulting in cerebral effects. This is most likely to occur when a new catheter or pump is implanted or during surgical revision of a catheter or implantable pump in cases of malfunction. A report of coma after implantation of a baclofen pump in five out of nine consecutive children illustrates this [ ]. The authors suggested that these children should be monitored in the recovery room for 5 hours postoperatively, in order to cover both the peak effect of any baclofen bolus and the additive effects of other perioperative CNS suppressants, such as opioids, benzodiazepines, or sedative antiemetics. In another report of transient coma after perioperative intrathecal bolus administration it was shown that the management of this complication can require admission to an intensive care unit [ ].

Impairment of speech, memory, and mental acuity, associated with an abnormal electroencephalogram, has been described in a young patient taking normal doses (20 mg bd); gradual withdrawal restored the patient and electroencephalogram to normal [ ]. Abnormal electroencephalographic changes have also been reported in a patient with deteriorating multiple sclerosis who developed encephalopathy 48 hours after starting baclofen in low dosage (10 mg tds), but this patient also had renal impairment; withdrawal led to reversal of symptoms in this case [ ].

Epilepsy, progressing to status epilepticus, has been ascribed to baclofen (80 mg/day); the fits stopped on gradual withdrawal of the baclofen [ ]. In contrast to other reports, this patient had no history of seizures.

Concern has been raised that baclofen might be associated with new-onset seizures in children [ ]. Among 35 children with cerebral palsy aged 1–10 years, five developed new-onset seizures within 1–2.5 months after baclofen was started or the dose was increased (dosage range 0.36–1.5 mg/kg/day). While the authors admitted that young children with cerebral palsy have a significant risk of developing seizures independent of other factors, they still felt that there might be an association with baclofen. Indeed, studies in animals have suggested that baclofen may have proconvulsive properties [ ], and three clinical papers have linked baclofen to convulsions. In one of these, two patients with tonic–clonic seizures among 14 adolescents with baclofen intoxication were described [ ]. There were also cases of seizures in three adults with traumatic brain injury who were treated with intrathecal baclofen and in a patient with multiple sclerosis [ , ]. We conclude that baclofen has some proconvulsive properties, which rarely result in clinically important effects. In most of the reported cases baclofen was continued with concomitant antiepileptic medication.

An elderly patient with a 4-year history of Alzheimer’s disease developed chorea 2 weeks after starting a trial of baclofen [ ]. The dosage had been gradually increased to 15 mg tds. The chorea resolved within 24 hours after the baclofen was withdrawn. The authors suggested that the chorea might have resulted from the combination of the GABA-agonist drug and deficient cholinergic function in Alzheimer’s disease.

Recurrent transient global amnesia has been reported in a middle-aged woman after intrathecal baclofen [ ]. The episodes were reduced by fludrocortisone and terminated by sublingual glyceryl trinitrate. This association has not previously been reported.

Baclofen reduced hot and cold temperature perception in patients with spinal cord injuries [ ], consistent with experimental data in animals. This suggests a role for baclofen in the treatment of neuropathic pain. The authors did not comment on any potential adverse effects of reduced temperature perception.

Aseptic meningitis after intrathecal administration of baclofen has been reported but, as viral causes could not be ruled out, the causative role of baclofen was unclear [ ].

Radiculopathy occurred in two patients as complications of intrathecal baclofen therapy early after pump implantation. The first patient had pain at the level of S1 and the second at L5; relief was obtained from analgesic drugs in one and catheter replacement in the other [ ].

Psychological, psychiatric

Euphoria or depression can occur, and mania has been reported in a patient with schizophrenia [ ].

Psychosis has been attributed to baclofen in therapeutic doses [ ].

• A 32-year-old man took oral baclofen 10 mg bd for muscular spasms secondary to tetanus. After 4 weeks he developed third-person auditory hallucinations and persecutory and referential delusions without underlying mood symptoms. These symptoms resolved within 1 week of withdrawal of baclofen. Rechallenge resulted in re-emergence of the psychotic symptoms, which again disappeared after withdrawal.

Gastrointestinal

A possible effect of intrathecal baclofen on intestinal motility has been proposed [ ]. Triggered by two cases of paralytic ileus in patients receiving continuous intrathecal baclofen, the authors reviewed the case notes of 14 patients and summed the days without bowel movements before and after intrathecal baclofen therapy. Intestinal function deteriorated in 10 patients, was unchanged in one, and improved in three. They therefore advised that intestinal activity should be closely observed in patients receiving intrathecal baclofen. However, they felt that treatment could be continued, even in particularly sensitive patients, if prokinetic, laxative, or eubiotic drugs were used to promote peristaltic function.

Paralytic ileus has been reported in a 52-year-old man with tetraplegia after he had received baclofen 100 micrograms/day intrathecally for 4 days; the dosage of baclofen was reduced to lowest rate of flow and the ileus resolved after 15 days [ ].