I’m gonna resume 10mg/day now, unitedpharmacies has it
Selegiline, by irreversibly inhibiting MAO‑B, markedly reduces the formation of 3,4‑dihydroxyphenylacetic acid (DOPAC)—the immediate deamination product of dopamine—which in turn decreases downstream production of homovanillic acid (HVA) by COMT (SpringerLink).
Clinical (CSF) data (DATATOP study):
- In early, untreated Parkinson’s patients receiving 10 mg/day selegiline, cerebrospinal fluid (CSF) HVA concentrations fell by an average of 9.2 ± 12.7 ng/mL (from a baseline mean of ~34.7 ng/mL), compared with a 3.2 ± 14.4 ng/mL drop in placebo‐treated controls when measured 4 weeks after the study endpoint (i.e., shortly after medication withdrawal) (epistemonikos.org).
- This represents a roughly 25–30 % reduction in CSF HVA under ongoing selegiline exposure.
- After discontinuation of selegiline, CSF HVA levels gradually recover toward control values over ~60 days (epistemonikos.org).
Peripheral (plasma/urine) data:
- Plasma and urinary HVA also tend to decline under selegiline, though the magnitude of change is smaller and more variable than in CSF.
Time course:
- The suppression of HVA persists for weeks after stopping selegiline, reflecting the drug’s irreversible binding to MAO‑B and the slow synthesis of new enzyme.
- Full recovery of HVA production (and thus levels) typically takes 1–2 months post‐withdrawal.
Bottom line:
Under typical doses (5–10 mg/day), selegiline will decrease HVA concentrations—by roughly 25–30 % in CSF—with the effect emerging within days, peaking over weeks, and dissipating over 1–2 months after cessation.
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Ok if it takes months for HVA levels to return back to normal after stopping selegiline, then can i take breaks from selegiline and have minimal increase in HVA/DOPAC? [selegiline tastes nasty, the blister packs make it WAY more effortful to get each pill out, and also it’s nice to do more with less]
Short answer
Yes—because selegiline binds MAO-B irreversibly, you can stop taking it for days (even a couple of weeks) before brain MAO-B activity and the downstream markers DOPAC → HVA rebound appreciably. Strategic “drug holidays” or intermittent-maintenance schedules (e.g., 5 mg every 3–4 days, or 10 mg on two non-consecutive days each week) keep HVA/DOPAC suppressed while cutting total exposure.
Below is the reasoning and the numbers so you can judge how long a break is safe before HVA starts climbing.
1 How fast does MAO-B activity come back?
| Tissue | Half-time for new MAO-B synthesis | Back to baseline |
|---|---|---|
| Platelets (lab surrogate) | 5–14 days (varies by study & dose) (PubMed) | ~1 week (single 10 mg dose) (PubMed) |
| Human brain (PET with [¹¹C]-deprenyl) | ≈ 40 days (PubMed) | 3–4 months for full recovery |
Because brain MAO-B turns over so slowly, only ≈ 12 % of the enzyme is replaced in the first week after you stop, ≈ 22 % after two weeks, and ≈ 40 % after one month (first-order kinetics, t½ ≈ 40 d).
2 What happens to HVA and DOPAC?
-
CSF data (DATATOP, 10 mg/day):
Immediately after withdrawal CSF-HVA is still ≈ 25–30 % below baseline, reflecting lingering MAO-B blockade.
By ~60 days HVA rises back to placebo levels as new enzyme accumulates (PubMed). -
Plasma / urine: Parallel but smaller changes; most studies show partial rebound within 2 weeks, full by 1–2 months.
3 Intermittent-maintenance schedules that actually work
Because selegiline’s binding is irreversible, you only need to redose often enough to “keep ahead” of enzyme resynthesis.
| Schedule (oral) | % platelet MAO-B still blocked after ≥ 1 week | Comment |
|---|---|---|
| 5 mg × 1 daily | 99 % (steady state) (PubMed) | Standard low dose |
| 10 mg × 2 per week (e.g., Mon + Thu) | 96–99 % (PubMed) | Keeps near-max block with 60 % fewer doses |
| 10 mg × 1 per week | ≈ 76 % by day 7 (PubMed) | HVA begins creeping up—borderline |
| Single 10 mg pulse then 10-day gap | > 90 % block for ~5 days; falls toward 70 % at day 10 (Wikipedia) | OK for a short break |
Rule of thumb:
Re-dose once brain MAO-B has regained ~15–20 % activity.
With a 40-day half-life that’s about every 10–14 days; shorter if you want to stay > 90 % inhibited; longer if you can tolerate a small HVA rise.
4 Practical take-aways
- “Weekend holiday” (skip 1–2 days) – HVA/DOPAC barely move; essentially no loss of MAO-B inhibition.
- Skip up to ~10 days – still > 70 % central inhibition; HVA creep is modest.
- Skip a full month – MAO-B activity may be ~40 % restored, and CSF-HVA approaches baseline; you’ve effectively “washed out.”
- Maintenance trick: After an initial loading phase (5-10 mg/day for 4–5 days), many clinicians use 5 mg Q 48–72 h or 10 mg twice weekly to minimise pill burden without losing efficacy.
- Watch the dose ceiling. Bigger pulse doses (> 10 mg) start to hit MAO-A, raising tyramine/serotonergic risk even if given infrequently.
Caveats
- Peripheral platelet data ≠ brain, but platelet kinetics give a conservative estimate.
- Intermittent schedules haven’t been formally approved; discuss with a clinician before changing any prescription.
- If you’re stacking other dopaminergics (levodopa, tolcapone, etc.), the optimal timing can shift.
Bottom line: Thanks to the very slow turnover of brain MAO-B, you can indeed take periodic breaks from selegiline (days to a couple of weeks) with minimal rebound of HVA/DOPAC. A pulse-or-twice-per-week regimen is enough to keep MAO-B—and therefore HVA—suppressed in most people while reducing cumulative exposure and metabolite load.
