No medication
- A signal arrives. Nerve cells pass messages across a tiny gap called a synapse. When a signal reaches the end of the sending cell, it releases packets of a chemical messenger, a neurotransmitter, into the gap.
- The message lands. The messenger drifts across and briefly fits into receptors on the receiving cell, like a key in a lock. That changes how likely the receiving cell is to fire.
- Cleanup. The sending cell pulls most of the messenger back in through a pump called a transporter, so it can be reused. Enzymes break down some of the rest. This keeps each signal short and crisp.
What's known and what isn't: This is a simplified teaching model, not a to-scale picture. The gap in a real synapse is thousands of times narrower than a human hair, and a single nerve cell can connect with thousands of others.
Sources: National Institute of Mental Health. Mental health medications.
SSRIs
- The recycling pump is blocked. SSRIs (selective serotonin reuptake inhibitors) block the serotonin transporter, the pump that pulls serotonin back into the sending cell.
- Serotonin stays in the gap longer. With the pump slowed, serotonin lingers in the synapse and has more chances to reach receptors. This happens within hours of the first dose.
- The brain adapts over weeks. Some improvement can start in the first 1 to 2 weeks, but the full benefit often takes 4 to 8 weeks or longer. That delay suggests the benefit comes from slower changes the brain makes in response, not from the extra serotonin itself.
What's known and what isn't: FDA labels describe the antidepressant effect as "presumed to be linked" to blocking serotonin reuptake; the full mechanism isn't known. Depression isn't simply "low serotonin." A 2022 umbrella review (published in print in 2023) found no consistent evidence for that idea, even though SSRIs do outperform placebo on average.
Examples: Sertraline, Escitalopram, Fluoxetine · Read the full class guide
Sources: Lexapro (escitalopram) prescribing information, section 12.1.; Moncrieff J, et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2023.; Cipriani A, et al. Comparative efficacy and acceptability of 21 antidepressant drugs. Lancet. 2018.
SNRIs
- Two pumps are blocked. SNRIs block the transporters for both serotonin and norepinephrine, so both messengers stay in the synapse longer.
- Why norepinephrine matters. Norepinephrine is involved in alertness, energy, and the body's pain-dampening pathways. That's one reason duloxetine is also approved for some nerve and musculoskeletal pain conditions.
- Same slow timeline. Like SSRIs, the mood benefit builds over weeks as the brain adapts.
What's known and what isn't: The duloxetine and venlafaxine labels say the exact mechanism is unknown and is believed to relate to boosting serotonin and norepinephrine activity.
Examples: Duloxetine, Venlafaxine · Read the full class guide
Sources: Cymbalta (duloxetine) prescribing information, section 12.1.; Effexor XR (venlafaxine) prescribing information, section 12.1.
Bupropion
- A different pair of messengers. Bupropion is a relatively weak blocker of the norepinephrine and dopamine transporters. It doesn't block serotonin recycling.
- Why that matters in practice. Because it leaves serotonin alone, bupropion has a different side effect pattern from SSRIs, with less sexual dysfunction and weight gain for most people.
What's known and what isn't: The bupropion label says its mechanism is unknown and presumed to involve norepinephrine and dopamine.
Examples: Bupropion · Read the full class guide
Sources: Wellbutrin XL (bupropion) prescribing information, section 12.1.
Benzodiazepines
- GABA is the brain's brake. GABA is the main calming messenger. When it binds its receptor (GABA-A), a channel opens and chloride flows into the receiving cell, making it less likely to fire.
- A second docking spot. Benzodiazepines don't replace GABA. They attach to a separate spot on the same receptor and make GABA work better, so the channel opens more often.
- Fast, and a real tradeoff. That's why they can ease anxiety quickly, often within an hour. The brain also adapts to them, which is why steady use can lead to dependence and withdrawal.
What's known and what isn't: Benzodiazepines are positive allosteric modulators of the GABA-A receptor. The FDA requires a boxed warning about abuse, misuse, addiction, dependence, and withdrawal, and about serious risks when combined with opioids.
Examples: Lorazepam, Clonazepam, Alprazolam · Read the full class guide
Sources: Griffin CE, et al. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013.; FDA. Boxed Warning updated to improve safe use of benzodiazepine drug class. 2020.
ADHD stimulants
- Blocking the pumps. Methylphenidate and amphetamines both block the transporters that recycle dopamine and norepinephrine.
- Amphetamines also push. Amphetamines go further: they also cause the sending cell to release more dopamine and norepinephrine, partly by running the transporter in reverse.
- Why it helps focus. These messengers help regulate attention and working memory in the brain's frontal areas. Unlike antidepressants, stimulants work within an hour or two of a dose.
What's known and what isn't: Both labels say the mode of therapeutic action in ADHD isn't known; they describe blocked reuptake and increased release of dopamine and norepinephrine.
Examples: Methylphenidate, Amphetamine salts, Lisdexamfetamine · Read the full class guide
Sources: Ritalin LA (methylphenidate) prescribing information, sections 12.1 and 12.2.; Adderall XR (mixed amphetamine salts) prescribing information, sections 12.1 and 12.2.; Faraone SV. The pharmacology of amphetamine and methylphenidate. Neurosci Biobehav Rev. 2018.
Antipsychotics (blockers)
- Covering the receptor. Most antipsychotics sit in the dopamine D2 receptor without switching it on, so dopamine can't land there. Newer ("atypical") ones also block serotonin 5-HT2A receptors.
- Turning down an overactive signal. In psychosis, brain imaging shows too much dopamine activity in a deep brain area called the striatum. Blocking D2 there reduces hallucinations and delusions.
- Why side effects happen. The same blocking in other dopamine pathways can cause stiffness or restlessness (movement pathway) and raised prolactin (hormone pathway). The dopamine map below shows where.
What's known and what isn't: Labels for quetiapine and clozapine describe the mechanism as unclear or unknown, but proposed to involve D2 and 5-HT2A antagonism. The dopamine finding in psychosis comes from brain imaging research (Howes and Kapur, 2009). One newer schizophrenia medication, xanomeline and trospium, works through muscarinic receptors rather than by blocking dopamine receptors.
Examples: Haloperidol, Risperidone, Olanzapine, Quetiapine, Xanomeline and trospium (different mechanism) · Read the full class guide
Sources: Seroquel (quetiapine) prescribing information, section 12.1.; Clozaril (clozapine) prescribing information, section 12.1.; Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III. Schizophr Bull. 2009.
Antipsychotics (partial agonists)
- Partly on, never fully on. Partial agonists fit the D2 receptor and switch it on part of the way. Think of a dimmer rather than an on/off switch.
- Down when high, up when low. Where dopamine is high, taking its place lowers the overall signal. Where dopamine is low, the partial signal is more than there was.
- Serotonin effects too. Aripiprazole and brexpiprazole also act on serotonin receptors (partial activation of 5-HT1A, blocking 5-HT2A), which may add to their effects in depression. The exact mix varies by drug; cariprazine, for example, acts most strongly at dopamine D3 and D2 receptors.
What's known and what isn't: The aripiprazole and brexpiprazole labels say the mechanism is unknown but could be mediated by partial agonism at D2 and 5-HT1A and antagonism at 5-HT2A.
Examples: Aripiprazole, Brexpiprazole, Cariprazine · Read the full class guide
Sources: Abilify (aripiprazole) tablets prescribing information, sections 1 and 12.1.; Rexulti (brexpiprazole) prescribing information, section 12.1.
Mood stabilizers
- Not one mechanism. "Mood stabilizer" describes what these medicines do, not how they work. Lithium and the anticonvulsants act in different ways.
- Calming overexcited cells. In lab studies, lamotrigine blocks voltage-sensitive sodium channels, which may steady the sending cell and reduce release of the excitatory messenger glutamate. The animation shows this idea. How it helps in bipolar disorder hasn't been established. Carbamazepine also acts on sodium channels, and its mechanism in bipolar disorder is likewise unknown. Valproate's mechanism isn't established either; one suggestion, for seizures, is that it raises brain GABA.
- Lithium works inside the cell. Lithium's mechanism is unknown. Research points to effects on signaling inside nerve cells, including enzymes called GSK-3 and inositol monophosphatase, but none is proven to be the reason it works.
What's known and what isn't: The lithium label says its mechanism as a mood stabilizer is unknown. The lamotrigine label proposes the sodium channel mechanism for its antiseizure action and says its relevance "remains to be established in humans." The valproate label says its mechanisms "have not been established."
Examples: Lithium, Lamotrigine, Valproate, Carbamazepine · Read the full class guide
Sources: Lithium carbonate prescribing information, section 12.1.; Lamictal (lamotrigine) prescribing information, sections 1 and 12.1.; Depakote (divalproex) prescribing information, section 12.1.; Malhi GS, et al. Potential mechanisms of action of lithium in bipolar disorder. CNS Drugs. 2013.