Objective This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies. Methods Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale‐Retrospective (BPSS‐R). Chi‐squared tests were conducted to assess specific prodromal symptoms, risk factors or markers of vulnerability between groups. Significant prodromal symptoms were entered in a stepwise forward logistic regression model. The probabilities of a gradual versus rapid onset pattern of the prodromes were computed with logistic regression models. Results The total sample included 108 patients (FEM = 72, FEP = 36). Social isolation was associated with the prodromal stage of a FEP whilst Increased energy or goal‐directed activity with the prodrome to a FEM. Physically slowed down presented the most gradual onset whilst Increased energy presented the most rapid. The presence of obstetric complications and difficulties in writing and reading during childhood were risk factors for FEP. As for markers of vulnerability, impairment in premorbid adjustment was characteristic of FEP patients. No specific risk factor or marker of vulnerability was identified for FEM. Conclusion Early characteristics differentiating FEP from FEM were identified. These findings might help shape early identification and preventive intervention programmes.

Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good number of agents, but differences in efficacy and safety profiles among these agents must be considered in order to tailor personalized therapies, especially when the long-term course of the illness is considered. There is wide room and need to ameliorate current pharmacological approaches to mania, but ongoing pharmacological research on the topic is scant. In this work we try to critically assess clinical factors and patients’ characteristics that may influence the treatment choice for manic episodes. In addition, we conduct a narrative review on experimental pharmacology of bipolar mania and psychotic disorders, presenting a critical overview on agents which could represent treatment alternatives for a manic episode in the next future. Results show limited novel or ongoing research on agents acting as mood stabilizers (Ebselen, Valnoctamide and Eslicarbazepine did not reach statistical significance in demonstrating antimanic efficacy). As for the emerging experimental antipsychotic, some of them (including KarXT, SEP-363856, RO6889450, ALKS3831) have demonstrated good antipsychotic efficacy and a favorable safety profile, but little is known about their use in patients with bipolar disorder and specifically designed trials are needed. Lastly, some benefits for the treatment of mania could be expected to come in the next future from non-mood stabilizers/non-antipsychotic agents (especially PKC inhibitors like Endoxifen): long-term trials are needed to confirm positive results in terms of long-term efficacy and safety.