Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine

Abstract

Cariprazine is currently approved for the treatment of patients with schizophrenia (USA and EU), and for manic, depressive, and episodes with mixed features in bipolar I disorder (USA): several randomized controlled studies have also explored its efficacy in patients with major depressive disorder. This review summarizes its current therapeutic uses and potential advantages for treating the main symptoms of schizophrenia, bipolar I and major depressive disorder, considering its pharmacodynamic properties, efficacy, and tolerability. Its predominantly D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, contributes to its efficacy across a wide array of psychopathological symptoms (including reality distortion, disorganized thought, negative symptoms, mood disturbance, anhedonia, and cognitive impairment), and to a favorable side effect profile. Cariprazine may be a “drug of choice” in patients with predominant negative and cognitive symptoms of schizophrenia, as well as those with metabolic syndrome. Further investigation of its relative efficacy when compared to aripiprazole or other active comparators is warranted. Its effectiveness in the treatment of bipolar mania, bipolar I depression and bipolar I episodes with mixed features, with minimal accompanying metabolic changes is well-established. The longer half-life and delayed time to relapse in patients diagnosed with schizophrenia when compared to other second-generation antipsychotics represent other advantages, given the high rates of non-adherence and frequent relapses seen in clinical practice. Its efficacy in overlapping symptom domains in other major psychiatric disorders appears promising.

Decreased plasma neuropeptides in first-episode schizophrenia, bipolar disorder, major depressive disorder: associations with clinical symptoms and cognitive function

“…The main reason for this lag behind is the lack of understanding of the diseases' etiopathology. Accumulating data from animal and human studies suggest that the pathophysiology of SCZ, BD and MDD are associated with monoamine abnormality (4)(5)(6)(7). The monoamine hypothesis is supported by the clinical efficacy of many drugs for treating mental illness, however, there is usually a time lag between the acute pharmacological effects and clinical improvement (8).…”

Decreased plasma neuropeptides in first-episode schizophrenia, bipolar disorder, major depressive disorder: associations with clinical symptoms and cognitive function

“…Furthermore, despite nosological speci city, these disorders can have shared mood disturbance (depression, euphoria, irritability, anhedonia, etc. ), psychotic symptoms (hallucinations, delusions), and cognitive impairment (executive function, and memory impairment) [7][8][9]. Research has suggested that dimensional representations may be more accurate representations than simple categorical descriptions when applied to the diagnosis of psychotic and non-psychotic disorders [10].…”

“…In addition to this diagnostic issue, the etiopathology of these diseases is not well understood. Accumulating data from animal and human studies suggest that the pathophysiology of SCZ, BD and MDD are associated with monoamine abnormality [7,[11][12][13]. Although the monoamine hypothesis is supported by the clinical e cacy of many drugs for treating mental illness, there is usually a time lag between the acute pharmacological effects and clinical improvement [14].…”

Design, Synthesis and Pharmacological Evaluation of Novel Conformationally Restricted N-arylpiperazine Derivatives Characterized as D2/D3 Receptor Ligands, Candidates for the Treatment of Neurodegenerative Diseases

“…The importance of dopaminergic pathways and receptor modulators in the control of neurodegenerative diseases led to the development of drugs such as the classical typical antipsychotic haloperidol ( 1 ), a D 2 receptor antagonist (Ki = 0.89 nM) [ 19 , 20 ], and the atypical antipsychotics aripiprazole ( 2 ) (Ki D 2 = 0.34 nM; Ki D 3 = 0.8 nM) and cariprazine ( 3 ) (Ki D 3 = 0.085 nM; Ki D 2 = 0.49 nM), as partial agonists of D 2 and D 3 receptors [ 21 , 22 , 23 , 24 , 25 , 26 ], approved for the treatment of schizophrenia and bipolar disorder ( Figure 1 ).…”