List of investigational bipolar disorder drugs

Preregistration

• Lurasidone (DSP-1349M; Latuda; SM-13496; SMP-13496) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders

Phase 3

• ALM-008 – undefined mechanism of action (mood stabilizer) – bipolar disorders
• Azetukalner (1OP-2198; encukalner; VRX-621698; XEN-1101; XPF-008) – K_v7.2 and K_v7.3 potassium channel opener – bipolar depression
• Brenipatide (LY-3537031) – glucagon-like peptide-1 (GLP-1) receptor agonist and gastric inhibitory polypeptide (GIP) receptor agonist – bipolar disorders
• Brexpiprazole (Lu-AF41156; OPC-34712; OPDC-34712; Rexulti; Rxulti) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• Cycloserine/lurasidone (Cyclurad; D-cycloserine/lurasidone; lurasidone/cycloserine; NRX-101) – combination of cycloserine (ionotropic glutamate NMDA receptor glycine site partial agonist) and lurasidone (atypical antipsychotic/non-selective monoamine receptor modulator) – bipolar depression
• Endoxifen (4-hydroxy-N-desmethyltamoxifen; Z-endoxifen) – selective estrogen receptor modulator (SERM) and protein kinase C (PKC) inhibitor – bipolar disorders
• Lumateperone (Caplyta; ITI-007; ITI-722) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• Risperidone extended release (LYN-005) – atypical antipsychotic (non-selective monoamine receptor modulator) – schizoaffective disorder
• SEP-4199 (non-racemic amisulpride; aramisulpride/esamisulpride [85:15 ratio]) – dopamine D₂ and D₃ receptor antagonist and serotonin 5-HT_2B and 5-HT₇ receptor antagonist – bipolar depression
• Xanomeline/trospium chloride (BMS-986510; Cobenfy; KarXT; LY-246708/trospium chloride) – combination of xanomeline (non-selective muscarinic acetylcholine receptor agonist) and trospium chloride (peripherally selective non-selective muscarinic acetylcholine receptor antagonist) – bipolar disorders

Phase 2/3

• Opakalim (BHV-7000; BPN-25203; KB-3061) – K_v7.2 and K_v7.3 potassium channel opener – bipolar disorders

Phase 2

• Aldesleukin (ILT-101; interleukin-2; IL2; IL-2) – recombinant interleukin-2 (IL-2) replacement (interleukin-2 receptor agonist) – bipolar disorders
• Amdiglurax (ALTO-100; NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator) – bipolar depression
• Brilaroxazine (RP-5000; RP-5063) – atypical antipsychotic (non-selective monoamine receptor modulator) – schizoaffective disorder
• Cenobamate (ONO-2017; Ontozry; senovamate; X-Copri; XCopri; YKP-3089) – voltage-gated sodium channel (VGSC) blocker and GABA release enhancer – bipolar disorders
• Desmethyl cariprazine prodrug (ABBV-932; RGH-932) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar depression, bipolar disorders
• Direclidine (HTL-0016878; NBI-1117568; NBI-568) – muscarinic acetylcholine M₄ receptor agonist – bipolar I disorders
• Ebselen (DR-3305; ebselene; ebseleno; ebselenum; harmokisane; PZ-51; SPI-1005; SPI-3005) – various actions – bipolar disorders
• Elunetirom (ABX-002) – thyroid hormone receptor beta (TRβ) agonist – bipolar depression
• Icalcaprant (ABBV-1354; CVL-354) – κ-opioid receptor antagonist – bipolar depression
• JNJ-8942 – undefined mechanism of action – bipolar disorders
• JNJ-18038683 – serotonin 5-HT₇ receptor antagonist – bipolar disorders
• JNJ-55308942 – purine P2X₇ receptor antagonist – bipolar depression
• Lithium cocrystal (AL-001-Alzamend Neuro; lithium salicylate/L-proline cocrystal) – undefined mechanism of action (mood stabilizer) – bipolar disorders, bipolar I disorders
• N-Methylamisulpride (LB-102) – dopamine D₂ and D₃ receptor antagonist and serotonin 5-HT_2B and 5-HT₇ receptor antagonist – bipolar depression
• Navacaprant (BTRX-140; BTRX-335140; CYM-53093; NMRA-140; NMRA-335140) – κ-opioid receptor antagonist – bipolar depression
• OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – dopamine D₂ receptor agonist, serotonin 5-HT_2A receptor agonist, and so-called "dopamine stabilizer" – bipolar depression
• Psilocybin (COMP360; COMP-360) – non-selective serotonin receptor agonist, serotonin 5-HT_2A receptor agonist, and psychedelic hallucinogen – bipolar depression
• RAP-219 – AMPA receptor negative allosteric modulator – bipolar disorders
• Vortioxetine (Brintellix; LU-AA21004; LuAA 21004; Trintellix; Vortidif) – serotonin reuptake inhibitor, serotonin 5-HT_1A and 5-HT_1B receptor agonist, and serotonin 5-HT_1D, 5-HT₃, and 5-HT₇ receptor antagonist – bipolar depression
• Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABA_A receptor positive allosteric modulator and neurosteroid – bipolar depression

Phase 1/2

• Cariprazine (cariprazine depot) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders

Phase 1

• Brilaroxazine (RP-5000; RP-5063) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• CB03-154 (CB-03; CB-003) – K_v7.2 and K_v7.3 potassium channel opener – bipolar disorders
• Scopolamine (DPI-385-CVS; DPI-386; DPI-386 Nasal Gel; DPI-386-SG; DPI-386-SS; DPI-387; DPI-521-CG; DPI-550-TBI; Inscop spray) – non-selective muscarinic acetylcholine receptor antagonist – bipolar depression

Clinical phase unknown

• LTX-001 – glutaminase inhibitor – bipolar disorders
• Quetiapine oral suspension – non-selective monoaminer eceptor modulator – bipolar disorders

Preclinical

• Estianeptine ((S)-tianeptine; TNX-4300) – peroxisome proliferator-activated receptor PPARβ/δ and PPARγ agonist

Research

• NORA-520 (NRT-023; brexanolone prodrug) – GABA_A receptor positive allosteric modulator and neurosteroid (brexanolone prodrug) – bipolar disorders

No development reported

• AMG-581 – undefined mechanism of action – schizoaffective disorder
• Aripiprazole controlled release (ZY-102) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• Aripiprazole transdermal (AQS-1301) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• AZD-4451 – undefined mechanism of action – bipolar disorders
• Cariprazine (MP-214; Reagila; RGH-188; Symvenu; Vraylar; WID-RGC20) – atypical antipsychotic (non-selective monoamine receptor modulator) – schizoaffective disorder
• Elpetrigine (GW293273; JZP-4) – volgate-gated sodium channel blocker and calcium channel blocker – bipolar disorders
• Esketamine (Falkieri; PG061; S-ketamine) – ionotropic glutamate NMDA receptor antagonist – bipolar depression
• Paliperidone controlled-release (DLP-115) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• Research programme: long-acting neuropsychiatric therapeutics - Teva (NP-201; NP-202; NP-202-Teva; NP201-Teva; risperidone long-acting implant; ropinirole long-acting implant) – monoamine receptor modulators – bipolar disorders
• SKL-PSY (FZ-016; SKL-PSY/FZ-016) – serotonin 5-HT_1A receptor agonist – bipolar disorders
• SPD-421 (DP-VPA) – voltage-gated sodium channel (VGSC) blocker, GABA transaminase (GABA-T) inhibitor, histone deacetylase inhibitor, other actions (valproic acid prodrug) – bipolar disorders
• SPN-802 – undefined mechanism of action – bipolar disorders
• Ziprasidone extended release (ziprasidone once-daily) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders

Suspended

• Uridine (RG-2417) – mitochondrial protein stimulant – bipolar disorders

Discontinued

• Armodafinil (CEP-10953; Nuvigil; R-modafinil) – atypical dopamine reuptake inhibitor (DRI) – bipolar depression
• Bifeprunox (DU-127090) – dopamine D₂ and D₃ receptor partial agonist and serotonin 5-HT_1A receptor partial agonist – bipolar disorders
• BL-1020 (AN-168; CYP-1020; perphenazine GABA ester; perphenazine-4-aminobutyrate) – dopamine receptor antagonist and GABA receptor agonist – schizoaffective disorder
• Eslicarbazepine acetate (Aptiom; BIA 2-093; Exalief; SEP-0002093; SEP-2093; Stedesa; Zebinix) – voltage-gated sodium channel (VGSC) blocker (eslicarbazepine prodrug) – bipolar disorders
• Gabapentin (CI-945; Gabapen; GOE-3450; Neurontin) – gabapentinoid (α₂δ voltage-dependent calcium channel blocker) – bipolar disorders
• Licarbazepine (GP-47779; LIC-477; licarbazapine) – voltage-gated sodium channel (VGSC) blocker
• Lisdexamfetamine (Elvanse; LDX; NRP-104; S-877489; SHP-489; SPD-489; Tyvense; Venvanse; Vyvanse) – norepinephrine–dopamine releasing agent (NDRA) – bipolar depression
• Lu AA39959 – ion channel modulator – bipolar depression, bipolar disorders
• Lu AF35700 – dopamine D₁ receptor modulator, serotonin 5-HT_2A receptor modulator, and serotonin 5-HT₆ receptor modulator – schizoaffective disorder
• MK-8189 – phosphodiesterase PDE10A inhibitor – bipolar disorders
• MP-101 (LY-2979165) – metabotropic glutamate mGlu₂ and mGlu₃ receptor agonist – bipolar disorders
• Oxcarbazepine (GP-47680; KIN-493; NPC-04; oxacarbazepine; TRI-476; Trileptal) – voltage-gated sodium channel (VGSC) blocker (licarbazepine prodrug) – bipolar disorders
• Oxcarbazepine extended-release – voltage-gated sodium channel (VGSC) blocker (licarbazepine prodrug) – bipolar disorders
• Paliperidone (9-hydroxyrisperidone; Invega; JNS-007ER; R0-76477; RO-76477) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders, manic episodes
• PF-04455242 (PF-4455242) – κ-opioid receptor antagonist – bipolar depression
• R-103 (ABS-103R; R-ABS-103; (R)-ABS-103) – "GABA receptor agonist" (valproic acid analogue) – bipolar disorders
• Radafaxine (GW-353162; bupropion metabolite) – norepinephrine–dopamine reuptake inhibitor (NDRI) – bipolar disorders
• Ralmitaront (NTX-2001; RG-7906; RO-6889450) – trace amine-associated receptor 1 (TAAR1) agonist – schizoaffective disorder
• Ramelteon (Rozerem; TAK-375; TAK-375SL) – melatonin MT₁ and MT₂ receptor agonist – bipolar depression, bipolar disorders
• Rapastinel (BV-102; GLYX-13; GLYX-13-peptide; GLYX-13-trifluoroacetate; TPPT-amide; TPPT-amide-trifluoroacetate) – ionotropic glutamate NMDA receptor glycine site partial agonist – bipolar depression
• Risperidone (risperidone LAI) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar disorders
• scyllo-Inositol (AZD-103; ELND-005; quercinitol; scyllitol; scyllocyclohexanehexol; scylloinositol) – undefined mechanism of action – bipolar disorders
• SEP-378608 – undefined mechanism of action – bipolar disorders
• SR-31742A (SR-31742) – sigma receptor modulator – manic episodes
• Topiramate (Epitomax; KW-6485; KW-6485P; MCN 4853; RWJ 17021; Topamax; Topimax; Topina) – various actions – bipolar disorders
• Vabicaserin (PF-05208769; PF-5208769; SCA-136) – serotonin 5-HT_2C receptor agonist – bipolar disorders
• Vixotrigine (BIIB-074; CNV-1014802; GSK-1014802; raxatrigine) – Na_v1.7 voltage-gated sodium channel (VGSC) blocker – bipolar disorders
• Vofopitant (GR-205171) – neurokinin NK₁ receptor antagonist – bipolar disorders
• Ziprasidone (CP-88059-01; CP-88059-1; Geodon; ME-2112; RQ-00000003; Zeldox) – atypical antipsychotic (non-selective monoamine receptor modulator) – bipolar depression
• Zonisamide (AD-810; AD-810N; CI-912; Excegran; Kinaplase; PD-110843; Tremode; Trerief; Zonegran) – various actions – manic episodes

Approved drugs

Off-label drugs

• α₂-Adrenergic receptor agonists (e.g., clonidine, dexmedetomidine) (for acute agitation)^[2][3][4][5]
• Anticonvulsants (e.g., carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, pregabalin, tiagabine, topiramate, zonisamide)^[6][7]
• Antidepressants (for bipolar depression—but may cause manic or rapid cycling switches)^[8]
• Antipsychotics (e.g., haloperidol, chlorpromazine, perphenazine, fluphenazine, zuclopenthixol, loxapine)^[9][10]
• Benzodiazepines (e.g., diazepam, clonazepam, lorazepam) (for acute agitation)^[2][11]
• κ-Opioid receptor agonists (KOR agonists) (e.g., pentazocine) (for acute mania)^[12][13][14]
• Tamoxifen – selective estrogen receptor modulator (SERM) and protein kinase C (PKC) inhibitor^[15][16]