Drug intelligence / Profile preview

sertraline + ziprasidone

Development stage
Phase 2
Lead developer
Pfizer
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules
Administration
Oral
01

Overview

Sertraline + ziprasidone is a combination of two pharmaceutical drugs, sertraline (a selective serotonin reuptake inhibitor antidepressant) and ziprasidone (an atypical antipsychotic). This combination has been studied primarily in the context of schizophrenia, particularly for first-episode or treatment-resistant patients. The rationale for combining these agents is to allow for a lower dose of ziprasidone—thereby reducing its adverse effects—while maintaining or improving efficacy against both psychotic and depressive symptoms. Clinical trials have shown that this combination can lead to greater improvements in psychiatric symptoms, depressive symptoms, and psychosocial functioning compared to standard-dose ziprasidone monotherapy, with fewer side effects[2][4][5]. However, co-administration increases the risk of serious adverse events such as QT prolongation (irregular heart rhythm) and serotonin syndrome due to additive serotonergic activity[1][3][6].

02

Targets

HTR1A (Serotonin receptor 1A (5-hydroxytryptamine receptor 1A))HTR2A (5-hydroxytryptamine receptor 2A)HTR2C (5-hydroxytryptamine 2C receptor)SIGMAR1 (Sigma non-opioid intracellular receptor 1)NET (Norepinephrine Transporter)DAT (Dopamine plasma membrane transport protein)SERT (Sodium-dependent serotonin transporter)DRD2 (Dopamine D2 Receptor)HTR2A (Serotonin receptor 5-HT2A)

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