Table 1.
Therapeutic agents for the treatment of depression.
| Drug | Mechanism | Response time | Clinical Use |
|---|---|---|---|
| Early agents: Tricyclic Reuptake Inhibitor (RI), Monoamine oxidase inhibitor (MAOI), others | |||
| Imipramine | NE/5HT RI | weeks-months | FDA approved |
| Amitriptyline | NE/5HT RI | weeks-months | FDA approved |
| Desipramine | NE RI | weeks-months | FDA approved |
| Doxepin | NE RI/H1 antagonist | weeks-months | FDA approved |
| Amoxapine | NE/5HT RI/DA antagonist | weeks-months | FDA approved |
| Protriptyline | NE/5HT RI | weeks-months | FDA approved |
| Maprotiline | NE RI/H1 antagonist | weeks-months | FDA approved |
| Trimipramine | 5HT RI/ H1 antagonist | weeks-months | FDA approved |
| Tranylcypromine | MAOI | weeks-months | FDA approved |
| Phenelzine | MAOI | weeks-months | FDA approved |
| Isocarboxazid | MAOI | weeks-months | FDA approved |
| Selegiline | MAOI (MAO-B) | weeks-months | FDA approved |
| Bupropion | NE/DA RI | weeks-months | FDA approved |
| Trazadone | 5HT2A antagonist/5HT RI | weeks-months | FDA approved |
| Nefazodone | 5HT2A antagonist /5HT RI | weeks-months | FDA approved |
| Mirtazapine | α2AR/5-HT2A antagonist | weeks-months | FDA approved |
| Later generation reuptake inhibitors | |||
| Fluoxetine | SSRI | weeks-months | FDA approved |
| Sertraline | SSRI | weeks-months | FDA approved |
| Citalopram | SSRI | weeks-months | FDA approved |
| Paroxetine | SSRI | weeks-months | FDA approved |
| Vortioxetine | SSRI/variable 5HT effects | weeks-months | FDA approved |
| Vilazodone | SSRI/5HT1A partial agonist | weeks-months | FDA approved |
| Duloxetine | NE/5HT dual RI | weeks-months | FDA approved |
| Venlafaxine | NE/5HT dual RI | weeks-months | FDA approved |
| Levomilnacipran | NE/5HT dual RI | weeks-months | FDA approved |
| Atypical Antipsychotics (approved for use as add-on therapies for patients already taking an SSRI) | |||
| Quetiapine+SSRI | 5HT2/D2 antagonist | days-weeks | FDA approved |
| Olanzapine+fluoxetine | 5HT2/D2 antagonist | days-weeks | FDA approved |
| Aripiprazole+SSRI | 5HT2 antag/D2 partial agonist | days-weeks | FDA approved |
| Brexpiprazole+SSRI | 5HT2 antag/D2 partial agonist | days-weeks | FDA approved |
| Brain Stimulation Modalities | |||
| ECT | BDNF, circuit plasticity | weeks | FDA approved |
| TMS | Circuit plasticity | weeks-months | FDA approved |
| VNS | Circuit plasticity | months | FDA approved |
| Rapid Acting Agents | |||
| Ketamine | NMDA channel blocker | hrs-days | clinical trials |
| Lanicemine | NMDA channel blocker | hrs-days | clinical trials |
| CP 101,606 | NMDA-NR2B NAM | hrs-days | clinical trials |
| GLYX-13 | NMDA-Glycine NAM | hrs-days | clinical trials |
| AV-101 | NMDA-Glycine modulator | unknown | clinical trials |
| Scopolamine | ACh-muscarinic antagonist | hrs-days | experimental |
| Other novel treatments | |||
| Tianeptine | restores glutamate balance | weeks-months | EMA approved |
| ALKS-5461 | κ–opiate antagonist | weeks-months | clinical trials |
| L-Methylfolate | cofactor monoamine synthesis | weeks-months | dietary supplement |
| SAM-e | methyl group donor | weeks-months | dietary supplement |
| Acetyl-l-carnitine | fatty acid transfer | weeks-months | dietary supplement |
FDA approved, for depression; EMA, European Medicines Agency; NE, norepinephrine; 5-HT, serotonin; DA, dopamine; H1, histamine H1 receptor; SSRI, selective serotonin RI; D2, dopamine D2 receptor; ECT, electroconvulsie therapy; TMS, transcranial magnetic stimulation; VNS, vagal nerve stimulation; NAM, negative allosteric modulator; ACh, acetylcholine; SAM-e, S-adenosyl-methionine.