Long-acting mood stabilizers. The rationale for long-acting mood stabilizers is the same as for long-acting antidepressants. Patients with bipolar disorder are known to stop taking their medications because they miss their “highs.” Some long-acting antipsychotics are approved for bipolar disorder, but these are often associated with adverse effects, such as metabolic dysregulation, extrapyramidal symptoms, and tardive dyskinesia. Mood stabilizers are essential for the bipolar spectrum.
A “real” treatment for alcohol use disorders that eliminates craving for alcohol. Alcoholism is associated with more than 100 medical complications and is one of the leading causes of disability in the world. It is frustrating that very few drug companies have focused on this widely prevalent brain disorder, which is also a common comorbid condition in many psychiatric syndromes.
Treatment-resistance pharmacotherapy solutions. All psychiatric syndromes are heterogeneous and contain ≥1 subgroups (biotypes) that fail to respond to what is considered the “standard” psychopharmacologic treatment (such as antipsychotics, antidepressants, mood stabilizers, or anti-obsessive medications). Technically, those so-called treatment-resistant subtypes need medications with a different mechanism of action. For example, clozapine for treatment-resistant schizophrenia and ketamine for treatment-resistant depression provide proof that treatment resistance is treatable but by a mechanism of action that is completely different from that of standard therapies, such as N-methyl-D-aspartate (NMDA) receptor modulation. And there is a need for more than one pharmacotherapy for treatment resistance because some patients do not respond to either clozapine or ketamine.
Negative symptoms of schizophrenia cause significant functional disability and are well known to be a major unmet need. Some promising data are emerging on agents such as pimavanserin, cariprazine, and roluperidone, which is encouraging, but nothing is approved yet.
Cognitive deficits of schizophrenia, both neurocognition and social cognition, are another major unmet need that impair function in many patients. Many attempts to develop a pharmacologic treatment for these serious cognitive impairments have been made, but several candidates that initially appeared promising have bitten the dust. A focus on modulating the glutamate NMDA receptor may eventually lead to a breakthrough, and that may also help patients with bipolar disorder and major depressive disorder, both of whom also have cognitive deficits in several domains, albeit less severe than those experienced by patients with schizophrenia.
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