Abstract
The present patient was a 32-year-old man with a 2 year history of paranoid schizophrenia. Significant medical history of note was mitochondrial myopathy diagnosed 11 years previously. After his first presentation to hospital with psychotic symptoms (persecutory delusions), the patient was started on oral risperidone. He responded well to this initially, but became non-compliant with this medication after 1 year. For several weeks leading up to his second admission, the patient became increasingly psychotic with persecutory delusions and in this context was aggressive and threatening towards family and neighbours. On admission he was recommenced on oral risperidone and he improved slowly over the next few weeks. The option of risperidone depot was considered at the time to address his issue of non-compliance. Due to his existing myopathy, neurology opinion was sought, because it was unknown if repeat injury through i.m. injection would have an adverse effect, due to possible muscle regenerative issues. Consequently the decision was made to continue on oral risperidone with close follow up in the outpatient setting. Because there was lack of firm evidence about the possible effects of an i.m. antipsychotic on a patient with myopathy, we conducted the following literature review to aid with further management of this patient and any similar future cases.
Mitochondrial disorders are the most prevalent group of inherited neurometabolic diseases [1]. These are commonly due to a mutation in the mitochondrial DNA which can occur de novo, or be passed from maternal mitochondria [2]. Mitochondria are responsible for aerobic metabolism and production of the energy form adenosine triphosphate. Consequently the most commonly affected organ systems are those that rely most on aerobic respiration, such as the nervous system, heart, endocrine organs and skeletal muscle. Many patients have multi-system disease affecting several of these organs, while others have only one system involved [2]. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke (MELAS) is the most common mitochondrial syndrome and can present with a range of neuropsychiatric symptoms, including mood disorders and psychotic symptoms [3]. Myopathy can occur in isolation in mitochondrial disease, preferentially affecting skeletal muscle. Clinically these myopathies have variable presentations but the common findings are weakness, wasting and exercise intolerance. Muscles particularly affected are the proximal and extra-ocular muscles [2]. Despite progress in understanding of the pathophysiology of this disorder, there is currently no established treatment and management is largely supportive.
Certain myopathies are known to affect the regenerative capacity of skeletal muscle, such as the muscular dystrophies [4]. Normal skeletal muscle has a remarkable ability to regenerate after injury. Despite the mechanism of initial injury, muscle regeneration is characterized by two phases: a degenerative phase, with muscle fibre necrosis; and a regenerative phase, involving formation of new muscle fibres from muscle stem cells. In diseases associated with prolonged myofibre injury, the regenerative process fails to maintain normal skeletal muscle architecture [4]. Inadequate muscle regeneration, however, is not a feature in all myopathies, including mitochondrial myopathy. There has even been recent evidence to suggest that stimulating the normal degenerative–regenerative process, through exercised-induced myotrauma, may be of therapeutic benefit in mitochondrial myopathy [5].
Depot preparations are long-acting compounds given through i.m. injection. Risperidone depot formulation is an aqueous suspension microencapsulated into polyactide-coglycoglide polymers. This formulation results in a slow release of risperidone over several weeks [6]. Depot has several advantages over oral preparations, in that they improve compliance and eliminate bioavailability problems related to absorption and first-pass metabolism. Adverse effects at the injection site are rare but local reactions resulting in pain, redness, oedema, or abscess formation have been reported [6].
On the basis of this literature review, in general, depot antipsychotics can be utilized in patients with myopathy. Muscle regeneration is not affected in most myopathies (except for the muscular dystrophies) and therefore the minor trauma of injection is not a contraindication in this context. In the present patient the second trial of oral risperidone was successful but, if clinically indicated in the future, depot could certainly be used. The current information in the literature suggests that myopathy is not a definitive contraindication for the use of i.m. injection and in a clinical setting any potential risks should always be weighed against the benefits of a better controlled illness.