Box 1 Potential pharmacological and non-pharmacological strategies for treatment-resistant bipolar depression.
| Type of intervention | Mechanism of action or regions of stimulation |
|---|---|
| Pharmacological | |
| Aripiprazole | Partial agonist of D2, D3, D4, 5-HT1A, 5-HT2C, and 5-HT7 receptors31 |
| D-cycloserine | Partial agonist at the glycine recognition of the NMDA receptor35 |
| Ketamine | NMDA receptor antagonist34 |
| Lurasidone | Antagonist of 5-HT2A, 5-HT7, and D2 receptors, agonist of 5-HT1A receptor28 |
| AT1R blocker | Modulator of the renin-angiotensin system43 |
| Minocycline | Anti-microbial with anti-inflammatory and neuroprotective properties36 |
| Pioglitazone | Selective PPAR-γ agonist with anti-inflammatory properties38 |
| N-acetylcysteine | Decreases the oxidative stress caused by ROS through glutathione regulation42 |
| Non-pharmacological | |
| Non-invasive | |
| Deep TMS | Over the left dorsolateral PFC52 |
| iTBS | Over the left dorsolateral PFC51 |
| Magnetic seizure therapy | Over the bilateral PFC or the vertex50 |
| Invasive | |
| DBS | Bilateral subcallosal cingulate white matter60 |
| VNS therapy | Vagus nerve55 |
AT1R = angiotensin II type 1 receptor; DBS = deep brain stimulation; iTBS = intermittent theta-burst stimulation; NMDA = N-methyl-D-aspartate; PFC = prefrontal cortex; PPAR-γ = peroxisome proliferator-activated receptor-gamma; ROS = reactive oxygen species; TMS = transcranial direct-current stimulation; VNS = vagus nerve stimulation.