Migraine – Introduction
Some of you will know it has been my view for some time that the association between migraine and depression is closer than has generally been recognised. Evidence is now accumulating that this covers the genetics, pathophysiology and treatment of these two conditions.
The fact that both are common conditions does mean chance associations will be relatively common. Two epidemiological studies have both come up with similar statistics for an association between migraine, anxiety, and depression. That association is greater than can be explained by chance.
Merikangas’ prospective study suggests that for Migraineurs the lifetime course in 80% of cases is that anxiety precedes migraine, and in 75% depression succeeds migraine. A second large (but retro-spective) study produced reassuringly similar figures. Suicide attempt rates in migraineurs without depression were slightly elevated (7.1% vs 2.2% in controls); in migraine plus depression suicide attempt rate was high at 31.8%. This compared to depression alone at 16.5%.
Recent genetic studies further substantiate an association. These originate from Steven Peroutka who with Solomon Snyder just lost the race to ‘discover’ endorphins (to Hughes and Kosterlitz) and who then went on to become a leading world figure in 5-HT receptor sub-typing.
Their recent paper (Peroutka, S) about the genetics of depression and migraine concludes:–
‘These data indicate that migraine with aura, anxiety disorders, and major depression can be components of a distinct clinical syndrome associated with allelic variations within the DRD2 gene. Clinical recognition of this genetically based syndrome has significant diagnostic and therapeutic implications’.
This evidence suggests the wisdom of looking carefully for depressive symptoms in all those with migraine; it is logical that treatment decisions will be strongly influenced by co-morbidity.
Migraineurs without diagnosed depression may still have an increased risk of suicide.
When patients manifest both depression and migraine it is important to treat both conditions. It is useful to screen migraineurs for both past and family history of depression (especially bipolar disorder) and panic attacks. This will guide treatment. The association of migraine with bipolar disorder will influence antidepressant choice. for instance, Epilim may be considered for possible or definite bipolar cases.
This is a common problem and a fascinating area of therapeutics; it will reward your efforts with many grateful patients.
12. Meyer, JH, Goulding, VS, Wilson, AA, Hussey, D, et al., Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology, 2002. 163(1): p. 102-5.
13. Learned-Coughlin, SM, Bergstrom, M, Savitcheva, I, Ascher, J, et al., In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry, 2003. 54(8): p. 800-5.
14. Argyelan, M, Szabo, Z, Kanyo, B, Tanacs, A, et al., Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study. J Affect Disord, 2005. 89(1-3): p. 115-23.
15. Volkow, ND, Wang, GJ, Fowler, JS, Learned-Coughlin, S, et al., The slow and long-lasting blockade of dopamine transporters in human brain induced by the new antidepressant drug radafaxine predict poor reinforcing effects. Biol Psychiatry, 2005. 57(6): p. 640-6.
16. Owens, JM, Knight, DL, and Nemeroff, CB, [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine]. Encephale, 2002. 28(4): p. 350-5.
17. Yohn, SE, Collins, SL, Contreras-Mora, HM, Errante, EL, et al., Not All Antidepressants Are Created Equal: Differential Effects of Monoamine Uptake Inhibitors on Effort-Related Choice Behavior. Neuropsychopharmacology, 2016. 41(3): p. 686-94.
18. Ascher, JA, Cole, JO, Colin, JN, Feighner, JP, et al., Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry, 1995. 56(9): p. 395-401.
19. Carroll, FI, Blough, BE, Mascarella, SW, Navarro, HA, et al., Bupropion and bupropion analogs as treatments for CNS disorders. Adv. Pharmacol., 2014. 69: p. 177-216.
20. Gufford, BT, Lu, JB, Metzger, IF, Jones, DR, et al., Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo. Drug Metab. Dispos., 2016. 44(4): p. 544-53.
21. Benowitz, NL, Zhu, AZ, Tyndale, RF, Dempsey, D, et al., Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state. Pharmacogenet Genomics, 2013. 23(3): p. 135-41.
22. Talakad, JC, Kumar, S, and Halpert, JR, Decreased susceptibility of the cytochrome P450 2B6 variant K262R to inhibition by several clinically important drugs. Drug Metab. Dispos., 2009. 37(3): p. 644-50.
23. Molnari, JC, Hassan, HE, and Myers, AL, Effects of sertraline on the pharmacokinetics of bupropion and its major metabolite, hydroxybupropion, in mice. Eur. J. Drug Metab. Pharmacokinet., 2012. 37(1): p. 57-63.
24. Hoiseth, G, Haslemo, T, Uthus, LH, and Molden, E, Effect of CYP2B6*6 on Steady-State Serum Concentrations of Bupropion and Hydroxybupropion in Psychiatric Patients: A Study Based on Therapeutic Drug Monitoring Data. Ther. Drug Monit., 2015. 37(5): p. 589-93.
25. Laib, AK, Brunen, S, Pfeifer, P, Vincent, P, et al., Serum concentrations of hydroxybupropion for dose optimization of depressed patients treated with bupropion. Ther. Drug Monit., 2014. 36(4): p. 473-9.
26. Al-Abri, SA, Orengo, JP, Hayashi, S, Thoren, KL, et al., Delayed bupropion cardiotoxicity associated with elevated serum concentrations of bupropion but not hydroxybupropion. Clin Toxicol (Phila), 2013. 51(10): p. 1230-4.
27. Hayes, PE and Kristoff, CA, Adverse reactions to five new antidepressants. Clin. Pharm., 1986. 5(6): p. 471-80.
28. Balit, CR, Lynch, CN, and Isbister, GK, Bupropion poisoning: a case series. Med. J. Aust., 2003. 178(2): p. 61-3.
29. Salamone, JD, Pardo, M, Yohn, SE, Lopez-Cruz, L, et al., Mesolimbic Dopamine and the Regulation of Motivated Behavior. Curr Top Behav Neurosci, 2016. 27: p. 231-57.
30. Salamone, JD and Correa, M, The mysterious motivational functions of mesolimbic dopamine. Neuron, 2012. 76(3): p. 470-85.
31. Floresco, SB, Tse, MT, and Ghods-Sharifi, S, Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology, 2008. 33(8): p. 1966-79.
32. Randall, PA, Pardo, M, Nunes, EJ, Lopez Cruz, L, et al., Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences. PLoS One, 2012. 7(10): p. e47934.
33. Hosking, JG, Floresco, SB, and Winstanley, CA, Dopamine antagonism decreases willingness to expend physical, but not cognitive, effort: a comparison of two rodent cost/benefit decision-making tasks. Neuropsychopharmacology, 2015. 40(4): p. 1005-15.
34. Mai, B, Sommer, S, and Hauber, W, Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens. Cogn Affect Behav Neurosci, 2012. 12(1): p. 74-84.
35. Yohn, SE, Errante, EE, Rosenbloom-Snow, A, Somerville, M, et al., Blockade of uptake for dopamine, but not norepinephrine or 5-HT, increases selection of high effort instrumental activity: Implications for treatment of effort-related motivational symptoms in psychopathology. Neuropharmacology, 2016. 109: p. 270-80.
36. Yohn, SE, Gogoj, A, Haque, A, Lopez-Cruz, L, et al., Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040. Pharmacol. Biochem. Behav., 2016. 148: p. 84-91.
37. Frank, S, Tetrabenazine: the first approved drug for the treatment of chorea in US patients with Huntington disease. Neuropsychiatr Dis Treat, 2010. 6: p. 657-65.
38. Jankovic, J and Orman, J, Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology, 1988. 38(3): p. 391-4.
39. Kenney, C, Hunter, C, Mejia, N, and Jankovic, J, Is history of depression a contraindication to treatment with tetrabenazine? Clin. Neuropharmacol., 2006. 29(5): p. 259-64.
40. Kenney, C, Hunter, C, and Jankovic, J, Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov. Disord., 2007. 22(2): p. 193-7.
41. Baumeister, AA, Hawkins, MF, and Uzelac, SM, The myth of reserpine-induced depression: role in the historical development of the monoamine hypothesis. J Hist Neurosci, 2003. 12(2): p. 207-20.
42. van Praag, H, Asnis, GM, Kahn, RS, Brown, SL, et al., Monoamines and Abnormal Behaviour. A Multi-Aminergic Perspective. Br J Psychiatry, 1990. 157: p. 723-734.
43. van Praag, HM, Nosologomania: a disorder of psychiatry. World J Biol Psychiatry, 2000. 1(3): p. 151-8.