Guanfacine is actually shown to be just as effective for ADD as stimulants, hence the new long acting guanfacine version coming out from shire. Only problem is, most ADDers have low blood pressure (after all they tend to have low PEA, low vasopressin, low NE). Taking the full therapeutic dose of guanfacine would kill me for sure.
bgwithadd,
given that "Taking the full therapeutic dose of guanfacine would kill [you] for sure":
- would it be an option to take the full therapeutic dose of guanfacine with proven blood pressure increasers (which do not have to be neurostimulant medications) ?
- Guanfacine (along with Clonidine) is an Alpha-2 adrenergic receptor agonist. Prazosin is an Alpha-1 adrenergic receptor antagonist which also lowers blood pressure and also may be effective for ADHD (based on one study - see below). Do you have any comment on this?
[SCIENTIFIC AND CLINICAL REPORT SESSION 11-ADULT ADHD] No. 34 ALPHA-1 AGONIST PRAZOSIN FOR ADHD: THE ROLE OF NOREPINEPHRINE IN ADHD PATHOLOGY
Fletcher B. Taylor III, M.D., Rainier Associates, 5909 Orchard Street, West, Tacoma, WA 98467- 3824; Nancy Allison, P.D.
EDUCATIONAL OBJECTIVE: At the conclusion of the presentation, the participant should be able to understand the effects of d-amphetamine on alpha-1 adrenoceptors and their potential role in the pathophysiology of ADHD.
SUMMARY:
Objective: To explore the role of norepinepherine in the pathophysiology of ADHD and how D-amphetamine works for its treatment.
Methods: This double-blind, placebo-controlled study enrolled 16 ADHD adults, nine receiving ongoing d-amphetamine and seven not. They each received in a randomized fashion both placebo (lactose) and prazosin increased at .25 mg every one to two days to achieve optimal response. Measures included the ADHD Behavior Checklist for Adults (ADHD Checklist), the Clinical Global Impression of Improvement Scale (CGI), and the Stroop Color-Word Interference Test (Stroop). Adverse events were recorded.
Results:
For the prazosin-only group, the final mean dosage was 1.04 mg/ day (range .5-2 mg). Patient-rated CGI scores (p < .05) and Stroop performance scores (p < .05) were significantly improved on prazosin as compared with placebo. ADHD Checklist and Stroop performance improvements were significantly correlated. For the prazosin with d- amphetamine group, the mean dosage was 1.40 mg/day (range 5.0-2 mg). Prazosin offered no benefit over the placebo condition, and in fact all measures tended to worsen.
Conclusions: These preliminary data suggest that 1) noradrenergic alpha- 1 receptor activity may be important in ADHD pathophysiology, and 2) the change in alpha-1 receptor activity provided by d-amphetamine may be important in its efficacy for this disorder.
REFERENCES:
1. Shi WX, Pun CL, Zhang XX, Jones MD, Bunney BS: Dual effects of d-amphetamine on dopamine neurons mediated by dopamine and nondopamine receptors. J Neurosci 2000; 20:3504-11.
2. Arnsten AF, Mathew R, Ubriani R, Taylor JR, Li BM: Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function. Biol Psychiatry 1999; 45:26-31.
1: Eur J Pharmacol. 1996 Aug 1;309(1):1-11. Links
Prazosin inhibits MK-801-induced hyperlocomotion and dopamine release in the nucleus accumbens.
Mathé JM, Nomikos GG, Hildebrand BE, Hertel P, Svensson TH.
Department of Physiology and Pharmaccology, Karolinska Institutet, Stockholm, Sweden.
This study examined the putative inhibitory effect of the alpha 1-adrenoceptor antagonist prazosin (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)pip erazine) on changes evoked by the psychotomimetic, non-competitive NMDA receptor antagonist, MK-801((+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclohepten-5, 10-imine), in locomotor activity and extracellular concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens as assessed by microdialysis in freely moving rats. MK-801 (0.1 and 0.3 mg/kg, s.c.) induced a significant, dose-dependent increase in horizontal locomotor activity but did not affect rearing. Prazosin administration alone (1 mg/kg, s.c.) only slightly reduced horizontal activity during an initial 10 min measurement period, although it consistently reduced rearing. However, pretreatment with prazosin effectively suppressed the locomotor stimulation caused by either dose of MK-801 throughout the whole observation period, i.e. 40 min. Both doses of MK-801 significantly increased extracellular levels of dopamine in the nucleus accumbens up to approximately 90%. In addition, MK-801 dose dependently increased dopamine metabolite concentrations in the nucleus accumbens, but 5-HIAA was significantly increased only by the high dose of MK-801. When given alone, prazosin did not affect either dopamine, DOPAC, HVA or 5-HIAA levels. However, prazosin pretreatment effectively blocked MK-801-evoked increases in dialysate dopamine concentrations. Consequently, the potent and selective alpha 1-adrenoceptor antagonist prazosin was found to specifically suppress MK-801-evoked, but not basal dopamine release in the nucleus accumbens, while effectively blocking MK-801-evoked locomotor stimulation with only negligible effects on basal locomotor activity. Thus, alpha 1-adrenoceptor antagonism may act by reducing the sensitivity of the mesolimbic dopamine system to pharmacological or environmental challenge. Since most antipsychotic drugs exhibit both dopamine D2 receptor and alpha 1-adrenoceptor antagonistic properties, they may alleviate psychosis not only through blockade of postsynaptic dopamine receptors, but also presynaptically on the mesolimbic dopamine system, through their alpha 1-adrenoceptor antagonistic action. This latter action may contribute to reduce evoked dopamine hyperactivity, e.g. in response to stress.
PMID: 8864686 [PubMed - indexed for MEDLINE]
Edited by Visionary7903, 06 June 2009 - 12:04 PM.