The incidence of side effects with doxepin and its safety at these doses was similar to that of placebo in clinical trials; the most frequent side effects were headache and somnolence/sedation, both with an incidence of less than 5%. Other side effects sometimes associated with antihistamines, including daytime sedation, increased appetite, and weight gain, all were not observed. Clinical evidence of H1 receptor antagonists and TCAs for the treatment insomnia shows mixed effectiveness and is limited in its quality due to weaknesses like small sample sizes and poor generalizability. However, doxepin is a unique and notable exception; it has been well-studied in the treatment of insomnia and shows consistent benefits with excellent tolerability and safety. Aside from diphenhydramine and doxylamine, which have historical approval as hypnotics, doxepin is the only H1 receptor antagonist that is specifically approved for the treatment of insomnia in the United States.The effect sizes of very low-dose doxepin in the treatment of insomnia range from small to medium. These include subjective and objective measures of sleep maintenance, sleep duration, and sleep efficiency. Conversely, very low-dose doxepin shows relatively weak effects on sleep initiation and does not significantly separate from placebo on this measure. This is in contrast to benzodiazepines and nonbenzodiazepine (Z-drug) hypnotics, which are additionally effective in improving sleep onset latency. However, it is also in contrast to higher doses of doxepin (50 to 300 mg/day), which have been found to significantly reduce latency to sleep onset.
These cases have revealed that the cause of the disease likely exhibits genetic heterogeneity, meaning the disease involves mutations in other locations within the genome (although no other loci have been identified in the development of BD as of now). Diagnosis
Diagnosis of BD begins with clinical evaluation of individuals for characteristic symptoms of cramping and stiffness of exercised muscles. A few techniques are involved in confirming a diagnosis of BD.Blood testing may be used to measure serum creatine kinase, which ranges from normal to slightly elevated in those with BD. Skeletal muscle biopsies are used to examine muscle fibers. Biopsies in individuals with BD often show variation in muscle fiber size, atrophied fast-twitch muscle fibers, and increased nuclei number. Electromyography (EMG) can be used in diagnosis to rule out myotonia, or muscle stiffness that is detected by EMG. Individuals with BD have stiff muscles but normal EMG results (pseudo-myotonia), where no myotonic discharges are detected. Genetic testing may also be used in the diagnosis of BD to look for mutations in ATP2A1. Since only some forms of the disease are associated with ATP2A1, results of genetic testing do not always confirm a diagnosis of BD, but are useful to rule out other similar disorders. Treatment
There is no cure for BD, although treatment options are available for reducing the negative symptoms of BD. The drugs dantrolene and verapamil are used in BD treatment due to their effects on Ca2+.