Head to head
| Question | TMS | Spravato | Daily oral medicines | Trauma / talk therapy | ECT (context) |
|---|---|---|---|---|---|
| What is it, in one line? | Magnetic pulses exercise one brain circuit, in clinic | Glutamate-system nasal spray, in clinic, with a 2-hour watch | Chemical messenger adjustment, at home, every day | Structured retraining of memory, fear, and thinking, with a therapist | A brief, controlled seizure under anesthesia, in a hospital setting, on purpose |
| Best evidence for | Depression after failed medicine; OCD and anxious depression by machine | Treatment-resistant depression; fast relief of depressive symptoms in acute suicidal crisis (with an oral antidepressant) | Depression, anxiety, PTSD (sertraline/paroxetine approved), OCD, smoking (varenicline/bupropion/NRT) | PTSD — first-line, root treatment. Also first-line for anxiety disorders and a core depression treatment (CBT, behavioral activation, IPT) | The most powerful treatment known for severe, psychotic, catatonic, or imminently dangerous depression |
| How fast can it help? | Weeks 2–4 onward, gradual | Hours to days for some; judged at 4 weeks | 4–8 weeks at full dose (anxiety 8–12) | Weeks, building across a 12–16 session course | Often within 1–2 weeks of a course |
| Time burden | High: ~5 visits/week for ~6 weeks, ~19–40 min each, no recovery time | High: 2-hour-plus visits, 2x/week then weekly, plus a driver every time | Low daily burden, high daily discipline: a pill, every day, for months to years | One hour a week, plus homework that is the treatment, not an extra | Hospital visits 2–3x/week for weeks, anesthesia each time, escort required |
| Body-wide side effects | Essentially none — its signature advantage | Limited to treatment days mainly: dissociation, sedation, blood pressure rise | Yes — sexual, weight, stomach, sleep, sweating, blood pressure, depending on the family | Short-term emotional soreness as material is worked with; no physical effects | Headache, muscle aches, and memory effects — usually temporary, occasionally persistent |
| Driving afterwards | Yes, same hour | No — not until the next day, after sleep | Depends on sedation; most antidepressants, yes | Yes | No on treatment days; restrictions during a course |
| Dependence / withdrawal | None | Controlled medicine, misuse potential, given only in clinic — dependence managed by the REMS structure | Antidepressants: discontinuation syndrome if stopped abruptly (not addiction). Benzodiazepines: true dependence | None | None |
| What it cannot do | Cannot treat PTSD on standard machines; smoking only on BrainsWay Deep TMS; cannot work in one visit; cannot help a person who cannot attend | Cannot be taken at home; not approved for PTSD/anxiety alone; not shown to prevent suicide | Cannot work at a dose never reached or in a trial never completed; cannot, on average, resolve PTSD alone | Cannot proceed if avoidance wins every week — engagement is the active ingredient | Not a first step; reserved for severity, urgency, or failure of the rest, by design |
IV ketamine, placed honestly: off-label for depression (the drug is approved as an anesthetic), cash pricing at many clinics, protocols vary widely, evidence real but less standardized than Spravato's label program. Any IV ketamine proposal deserves the same screening, monitoring, and cost questions as Spravato, plus: “Why IV ketamine instead of the on-label Spravato, in my case, in writing?”
Rules that apply to almost every medicine below
- The clock: most antidepressants and anti-anxiety medicines need four to eight weeks at a full dose (anxiety often eight to twelve) before they can fairly be judged. A two-week trial at a starting dose is not a failed trial — it is an unfinished one.
- Stopping suddenly is its own problem: discontinuation syndrome — flu-like feelings, dizziness, “brain zaps,” nausea, irritability, vivid dreams. Worst: paroxetine and venlafaxine. Least: fluoxetine.
- Serotonin syndrome — too much serotonin activity — is rare but serious: agitation, confusion, fever, sweating, tremor, muscle stiffness, usually from combinations (an SSRI plus an MAOI, tramadol, linezolid, dextromethorphan, St. John's wort, or triptans in sensitive combinations). Every prescriber and pharmacist needs your full list, including over-the-counter products and supplements.
- Boxed warning: in trials of children, adolescents, and young adults, antidepressants raised suicidal thoughts and behaviors versus placebo. In practice, for any age: worsening agitation, restlessness, or suicidal thinking in the first weeks of a new antidepressant or dose increase is a call the prescriber now event.
- Mania switch: any antidepressant can push a person with bipolar disorder — diagnosed or not yet — into mania or a mixed state. A personal or family history of mania belongs in every intake, before any antidepressant, TMS course, or Spravato plan.
The medicine families
1. SSRIs — the usual starting point
Fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine. They keep more serotonin active between brain cells; benefit comes as circuits adapt over weeks. Good for: depression, anxiety disorders (broadest labels), PTSD (sertraline and paroxetine are the only FDA-approved PTSD medicines), OCD, PMDD. Pros: best overall safety record, once daily for most, generic and inexpensive, no dependence in the addiction sense; fluoxetine's long action forgives a missed dose and eases tapering. Cons: sexual side effects (a leading hidden reason people stop), early nausea, loose stools with sertraline, headache, sleep change, sweating, emotional blunting in some, modest weight gain (paroxetine most), discontinuation if stopped suddenly (paroxetine most, fluoxetine least), raised bleeding risk, low sodium in older adults. Citalopram has a dose cap for heart-rhythm reasons.
2. SNRIs — serotonin plus norepinephrine
Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran. The second messenger helps energy, focus, and the body's pain-volume control. Good for: depression including after an SSRI failed, GAD, panic, social anxiety, PTSD (venlafaxine is guideline-supported first-line), and for duloxetine: diabetic nerve pain, fibromyalgia, chronic muscle/bone pain. Pros: a real second mechanism; duloxetine's pain benefit is genuine and labeled. Cons: blood pressure and heart rate can rise (venlafaxine especially — BP must be checked), sweating, dry mouth, nausea, constipation, sexual effects like SSRIs, and the sharpest discontinuation syndrome of the families (venlafaxine). Duloxetine: avoid in significant liver disease and heavy alcohol use.
3. Bupropion — dopamine / norepinephrine, no serotonin
Wellbutrin; Zyban for smoking. Good for: depression (especially low energy, oversleeping, poor concentration, or SSRI sexual side effects — also used as an add-on for those), smoking cessation, seasonal depression prevention. Pros: no sexual side effects, weight-neutral to modest loss, energizing, no SSRI-type discontinuation syndrome, doubles as the smoking medicine. Cons: can worsen anxiety, agitation, and insomnia; seizure risk is dose-related — not with a seizure disorder or bulimia/anorexia; dry mouth, headache, tremor, can raise blood pressure. No PTSD or GAD label.
4. Mirtazapine — the sleep-and-appetite antidepressant
Blocks certain serotonin and adrenaline receptors while its antihistamine action produces sleepiness and appetite — side effects in one patient, the whole point in another. Lower doses tend to be more sedating. Good for: depression with insomnia, poor appetite and weight loss, nausea, prominent anxiety/agitation; often in older adults. Pros: helps sleep from the first night in many, few sexual effects, little nausea, combines usefully with SSRIs/SNRIs under prescriber direction. Cons: weight gain and sedation, sometimes substantial; dry mouth, constipation, cholesterol can rise; fever or sore throat on mirtazapine is a call-now symptom (rare lowered white cells).
Serotonin modulators — trazodone, vilazodone, vortioxetine, nefazodone
Trazodone: at low doses, a non-habit-forming sleep medicine in modern practice. Pros: cheap, no dependence, helps sleep the same night. Cons: morning hangover, dizziness and falls on standing, and priapism — a rare emergency. Vilazodone: SSRI plus a buspirone-like action; marketed on lower sexual effects (debated); stomach upset; must be taken with food. Vortioxetine: multi-action serotonin medicine with some of the better evidence for thinking and concentration symptoms in depression; nausea early is its main complaint; brand cost. Nefazodone: effective, few sexual effects, held in reserve by a rare serious liver-failure risk and heavy interactions.
5. Tricyclics (TCAs) — older, powerful, specialist-supervised
Amitriptyline, nortriptyline, imipramine, desipramine, doxepin, clomipramine. Good for: treatment-resistant depression (nortriptyline, with blood levels), clomipramine for OCD (one of the strongest ever made), low doses for nerve pain and migraine prevention, low-dose doxepin for insomnia. Pros: powerful where newer medicines failed, blood levels allow precision, cheap. Cons: dangerous in overdose — a two-week supply can be lethal to the heart, so small-quantity dispensing where suicide risk is active; heart-rhythm effects, sedation, falls, confusion in elders, dry mouth, constipation, blurred vision, urinary difficulty, weight gain, lowered seizure threshold, withdrawal if stopped abruptly. Not starting points.
6. MAOIs — the oldest family, the strictest rules
Tranylcypromine, phenelzine, isocarboxazid, selegiline (including the skin patch). They block the enzyme that breaks down serotonin, norepinephrine, and dopamine, so all three rise. Good for: deeply treatment-resistant depression, atypical depression, some resistant anxiety/panic in specialist hands. Pros: can work when nothing else has. Cons: the food and drug rules are safety rules — aged/high-tyramine foods can trigger a dangerous blood-pressure surge; many common medicines can trigger serotonin syndrome or a pressure crisis; washout periods of about two weeks (five for fluoxetine) are mandatory when switching; blood pressure can also drop on standing. Only prescribers experienced with MAOIs should run them. Tell surgery and anesthesia teams.
7. Add-on (augmentation) antipsychotics for depression
Aripiprazole, brexpiprazole, cariprazine, and quetiapine XR are FDA-approved as add-ons to an antidepressant for major depression; olanzapine + fluoxetine is approved for TRD. Pros: among the best-studied add-on strategies in TRD; can work within two to four weeks; choice can be matched to the profile (activating vs. sedating). Cons — read twice: metabolic effects (weight gain, blood sugar up to new diabetes, cholesterol rise — most with olanzapine and quetiapine; scheduled blood monitoring is required), movement effects (restlessness/akathisia, stiffness, and tardive dyskinesia — involuntary movements that can persist), sedation, rare impulse-control problems with aripiprazole. For PTSD they are not a main treatment and guidelines advise against antipsychotic monotherapy; for anxiety they are not first or second line.
Other augmentation strategies
Lithium add-on (strong older evidence in TRD, an anti-suicide record in mood disorders; blood-level, kidney, and thyroid monitoring, narrow safe range); thyroid hormone T3 add-on (modest evidence); buspirone add-on (comparable to bupropion augmentation in the large STAR*D study, gentler for some); combining two antidepressants from different families (common specialist practice, interaction stacking to watch); Auvelity (dextromethorphan + bupropion, approved 2022 — reaches into the glutamate neighborhood, faster onset in trials, taken at home; seizure, blood pressure, serotonin, and interaction rules apply); gepirone ER (approved 2023, marketed on lack of sexual dysfunction and weight neutrality; newer, brand cost).
8. Anti-anxiety and sedating medicines
| Medicine | Place | Pros | Cons |
|---|---|---|---|
| Buspirone | GAD; antidepressant add-on | Non-sedating, non-habit-forming, no withdrawal syndrome, weight and sexual neutrality | Slow — two to four weeks; two to three times a day; useless as a rescue for a panic surge; dizziness/nausea early |
| Benzodiazepines — alprazolam, clonazepam, lorazepam, diazepam, temazepam | Narrow, time-limited roles; certain medical uses | Fastest, strongest acute calming here — which is precisely the problem | Tolerance, dependence within weeks, withdrawal that can include seizures, memory harm, falls, crash risk, worsened sleep apnea, specifically not recommended in PTSD, interference with therapy learning, dangerous with opioids and alcohol. Never stop long-term use abruptly. |
| Hydroxyzine | Anxiety (labeled), as-needed calming, itch, sleep support | Non-habit-forming, inexpensive, flexible | Sedation, dry mouth, next-day grogginess, confusion risk in older adults, heart-rhythm caution in certain combinations |
| Gabapentin / pregabalin | Off-label anxiety (pregabalin labeled for GAD outside the U.S.); labeled for nerve pain, seizures, fibromyalgia (pregabalin) | Can settle body anxiety; helps pain-plus-anxiety or insomnia pictures | Sedation, dizziness, weight gain, misuse potential, withdrawal if stopped suddenly — taper; kidney dose adjustments |
| Beta-blockers (propranolol) | Off-label, performance anxiety — the physical surge only | Blocks shaking, pounding heart, tremor without sedation; taken before the event | Does nothing for worry itself; caution in asthma, low blood pressure/pulse, certain heart conditions, diabetes |
Mood stabilizers and sleep — in brief
Mood stabilizers (lithium, valproate, carbamazepine, lamotrigine, plus several antipsychotics with bipolar labels) treat and prevent mania and, for some, bipolar depression — the single most important diagnosis to sort out before stacking antidepressants or starting TMS or Spravato. If bipolar disorder is in the picture, the whole plan is rebuilt around mood stabilization first. Sleep: first-line for chronic insomnia is CBT-I therapy. Medicines encountered include low-dose trazodone, mirtazapine, and doxepin; melatonin and ramelteon; the “Z-drugs” (zolpidem, eszopiclone — dependence, next-day impairment, rare complex sleep behaviors with a boxed warning); and orexin blockers. Untreated sleep apnea mimics and worsens depression, nightmares, and anxiety — ask about a sleep study.