Efficacy and safety of botulinum toxin injection in reducing deltoid muscle hypertrophy.

With the increasing demand for body contouring, botulinum toxin (BTX) injection is being widely used off-label for muscular hypertrophy. However, to the best of our knowledge, no study has investigated the clinical efficacy of BTX type A (BTX-A) in deltoid muscle hypertrophy. This study was conducted to evaluate the efficacy and safety of intramuscular injection of BTX in reducing deltoid muscle hypertrophy. Overall, 10 patients with bilateral deltoid muscle hypertrophy were treated with an intramuscular injection of prabotulinum toxin A, with a total of 50 units [U] administered per patient. As measured by ultrasonography, the thickness of the deltoid muscles was significantly decreased at weeks 2 and 12. In addition, the clinical assessment score by blinded investigators was improved after the treatment; however, patients' satisfaction scores were relatively low. No major complications were reported. Therefore, intramuscular injection of BTX-A seems to be a candidate for novel treatment option for deltoid muscle hypertrophy. Further larger clinical studies are warranted to confirm the efficacy of BTX-A.

Treatment of acquired Brown syndrome in a child with a single intramuscular systemic depot steroid injection.

A 10-year-old girl presented with a complaint of diplopia and mild superomedial orbital pain in the left eye of 2 weeks' duration. She had limited elevation of the left eye, especially in adduction, moderate limitation of elevation in the primary position, mild limitation of elevation in abduction, downshoot in adduction, mild hypotropia in the primary position, and normal abduction. There was mild swelling and tenderness in the superomedial aspect of her left orbit. Fundus examination revealed intorsion of the left fundus on upgaze. She was diagnosed with acquired Brown syndrome, due presumably to a local inflammatory cause, and treated with a single intramuscular depot injection of betamethasone in her deltoid muscle. One week later, her symptoms were resolving, and there was marked improvement of elevation of the left eye in adduction, with near normal elevation in the primary position and in abduction. There was no recurrence 3 months later.

Statins Trigger Mitochondrial Reactive Oxygen Species-Induced Apoptosis in Glycolytic Skeletal Muscle.

AIMS: Although statins are the most widely used cholesterol-lowering agents, they are associated with a variety of muscle complaints. The goal of this study was to characterize the effects of statins on the mitochondrial apoptosis pathway induced by mitochondrial oxidative stress in skeletal muscle using human muscle biopsies as well as in vivo and in vitro models. RESULTS: Statins increased mitochondrial H2O2 production, the Bax/Bcl-2 ratio, and TUNEL staining in deltoid biopsies of patients with statin-associated myopathy. Furthermore, atorvastatin treatment for 2 weeks at 10 mg/kg/day in rats increased H2O2 accumulation and mRNA levels and immunostaining of the Bax/Bcl-2 ratio, as well as TUNEL staining and caspase 3 cleavage in glycolytic (plantaris) skeletal muscle, but not in oxidative (soleus) skeletal muscle, which has a high antioxidative capacity. Atorvastatin also decreased the GSH/GSSG ratio, but only in glycolytic skeletal muscle. Cotreatment with the antioxidant, quercetin, at 25 mg/kg/day abolished these effects in plantaris. An in vitro study with L6 myoblasts directly demonstrated the link between mitochondrial oxidative stress following atorvastatin exposure and activation of the mitochondrial apoptosis signaling pathway. INNOVATION: Treatment with atorvastatin is associated with mitochondrial oxidative stress, which activates apoptosis and contributes to myopathy. Glycolytic muscles are more sensitive to atorvastatin than oxidative muscles, which may be due to the higher antioxidative capacity in oxidative muscles. CONCLUSION: There is a link between statin-induced mitochondrial oxidative stress and activation of the mitochondrial apoptosis signaling pathway in glycolytic skeletal muscle, which may be associated with statin-associated myopathy.

Paliperidone Palmitate Long-Acting Injectable Given Intramuscularly in the Deltoid Versus the Gluteal Muscle: Are They Therapeutically Equivalent?

Paliperidone palmitate long-acting injectable is a second-generation antipsychotic indicated for the treatment of schizophrenia. According to the product monograph, the monthly maintenance dose of paliperidone palmitate can be given in either the deltoid or gluteal muscle. Unfortunately, many clinicians may misinterpret these directions to mean that these intramuscular sites are interchangeable, and thus therapeutically equivalent. Currently, the literature on this topic is sparse, but the published pharmacokinetic studies and Food and Drug Administration submission data on paliperidone palmitate show discrepancies in the elimination half-life, peak plasma concentration, and absorption rate that are dependent on the site of injection. The degree of shifts in pharmacokinetic parameters suggests that paliperidone palmitate injections via the deltoid and gluteal muscle are not bioequivalent and therefore are not therapeutically equivalent. Thus, using the same maintenance dosing regimen at both sites or switching between sites of injection may result in unforeseen consequences in patient outcomes.

Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia.

Aripiprazole lauroxil is a linker lipid ester of aripiprazole for extended-release intramuscular (IM) injection. This multicenter, randomized, open-label study evaluated the pharmacokinetics (PK), relative bioavailability, and tolerability of a single IM deltoid or gluteal injection of aripiprazole lauroxil in adult subjects with chronic stable schizophrenia or schizoaffective disorder. Forty-six subjects were randomized 1:1 to aripiprazole lauroxil 441 mg IM in the deltoid or gluteal muscle. Samples were collected through 89 days post-dose to measure levels of aripiprazole lauroxil, N-hydroxymethyl aripiprazole, aripiprazole, and dehydro-aripiprazole. Forty-three (93.5%) subjects completed all study assessments; most were CYP2D6 extensive or immediate metabolizers (96%); two (4%) were poor metabolizers. The PK of aripiprazole following aripiprazole lauroxil was characterized by a steady rise in plasma concentrations (Tmax 44-50 days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4-19.2 days). Deltoid vs. gluteal administration resulted in slightly higher Cmax aripiprazole concentrations [1.31 (1.02, 1.67); GMR 90% CI]; total exposure (AUCinf) was similar between sites of administration [0.84 (0.57, 1.24)]. N-hydroxymethyl-aripiprazole and dehydro-aripiprazole exposures were 10% and 33-36%, respectively, of aripiprazole exposure following aripiprazole lauroxil. The most common adverse events were injection site pain in 20 subjects (43.5%) and headache in 6 subjects (13.0%) of mild intensity occurring at a similar rate with deltoid and gluteal administration. Exposure ranges with deltoid and gluteal administration overlapped, suggesting that these sites may be used interchangeably. Despite a higher incidence of adverse events, deltoid muscle provides a more accessible injection site and could facilitate patient acceptance.

Deltoid, triceps, or both responses improve the success rate of the interscalene catheter surgical block compared with the biceps response.

BACKGROUND: The influence of the muscular response elicited by neurostimulation on the success rate of interscalene block using a catheter (ISC) is unknown. In this investigation, we compared the success rate of ISC placement as indicated by biceps or deltoid, triceps, or both twitches. METHODS: Three hundred (ASA I-II) patients presenting for elective arthroscopic rotator cuff repair were prospectively randomized to assessment by biceps (Group B) or deltoid, triceps, or both twitches (Group DT). All ISCs were placed with the aid of neurostimulation. The tip of the stimulating needle was placed after disappearance of either biceps or deltoid, triceps, or both twitches at 0.3 mA. The catheter was advanced 2-3 cm past the tip of the needle and the block was performed using 40 ml ropivacaine 0.5%. Successful block was defined as sensory block of the supraclavicular nerve and sensory and motor block involving the axillary, radial, median, and musculocutaneous nerves within 30 min. RESULTS: Success rate was 98.6% in Group DT compared with 92.5% in Group B (95% confidence interval 0.01-0.11; P<0.02). Supplemental analgesics during handling of the posterior part of the shoulder capsule were needed in two patients in Group DT and seven patients in Group B. Three patients in Group B had an incomplete radial nerve distribution anaesthesia necessitating general anaesthesia. One patient in Group B had an incomplete posterior block extension of the supraclavicular nerve. No acute or late complications were observed. CONCLUSIONS: Eliciting deltoid, triceps, or both twitches was associated with a higher success rate compared with eliciting biceps twitches during continuous interscalene block.

Patients' acceptance of the deltoid application of risperidone long-acting injection.

OBJECTIVE: Recently risperidone long-acting injection (RLAI) was approved for alternative injection into the deltoid muscle in addition to the already established injection into the gluteal muscle. For the first time two different injection locations of a long-acting antipsychotic injection can be offered to patients. Their actual acceptance is of key interest. EXPERIMENTAL PROCEDURES: We surveyed 60 patients stabilized on gluteal RLAI therapy in our depot outpatient clinic. Participants were offered the possibility of switching to the alternative deltoid injection in a standardized manner. Prior to switching patients scored the extent of perceived pain and experienced level of shame through the present gluteal injection therapy on a 7-point-scale. Patients choosing to switch were followed up after three months and asked to report on their individual experience. RESULTS: Switching to the deltoid application was chosen by 34 out of 60 patients. Three months later 15 patients were still receiving deltoid injections. The main reason for their staying with the deltoid injection was improved practicability as reported by these patients and 13 out of 15 patients clearly preferred the new location over the gluteal application. The main reason for returning to the gluteal injection was the pain experienced through the injection in the deltoid. Patients' initial decision whether to switch was not correlated with either perceived pain or the experienced level of shame through the preceding gluteal injections. CONCLUSIONS: The application of RLAI in the deltoid muscle is viewed as an alternative to the injection in the gluteal muscle by a considerable number of patients. Nevertheless, some patients experience increased injection pain through this application location while others perceive the switch as beneficial in terms of practicability. Therefore offering both injection locations with their respective pros and cons should become standard in the RLAI treatment offered.

Risperidone long-acting injection: pharmacokinetics following administration in deltoid versus gluteal muscle in schizophrenic patients.

Long-acting injectable (LAI) risperidone for intramuscular injection into the gluteal muscle every 2 weeks is approved for schizophrenia. The deltoid muscle provides a more accessible injection site and could therefore facilitate patient acceptance of an injectable medication. Two studies in chronic schizophrenic subjects evaluated the pharmacokinetics and tolerability of LAI risperidone administered into the deltoid muscle. The pharmacokinetics following deltoid injection and bioequivalence between deltoid and gluteal administration were assessed in an open-label, single-dose, crossover, fully powered bioavailability study. Tolerability and safety of deltoid LAI risperidone were investigated in an open-label multiple-dose study in subjects who were previously being treated with gluteal injections of LAI risperidone. Patients received 4 sequential intramuscular injections of LAI risperidone, administered every 2 weeks into the deltoid muscle. Deltoid and gluteal injections of LAI risperidone were shown to be bioequivalent at equal doses with respect to peak and total plasma exposure and exhibited dose-proportional pharmacokinetics, independent of injection site. In addition, deltoid injection was safe and well tolerated. Injection of LAI risperidone into the deltoid muscle can be considered an alternative route of administration, because deltoid and gluteal injections are interchangeable in terms of drug exposure, with no additional safety or tolerability issues.