NERVOUS SYSTEM

Stress/mild anxiety

| Practice points|

• B complex vitamins may support stress and mood, and are well tolerated• Kava may be benefi cial for anxiety and stress states. Long-term use should be monitored• Passionfl ower and chamomile may have mild anxiolytic activity however clinical data are limited• The role of fi sh oil in anxiety is unclear, although omega-3s are known to have multiple roles in cognitive health

| Primary recommendations |

B-COMPLEX VITAMINS

Mechanism of action• Folate, B6 and B12 have a role in neural health and energy metabolism.7 They are also involved in the metabolism of the potentially toxic amino acid homocysteine (Hcy) to methionine. High Hcy and low B vitamins may be associated with poorer cognitive function and neurodegenerative disorders.7,8 Chronic stress depletes B67

• Several B vitamins are integral to the synthesis of neurotransmitters and catecholamines that are essential for psychological wellbeing, including serotonin and dopamine8,9

Research• 2 double-blind randomised controlled trials (RCTs) assessing effects of B complex-containing multivitamins on mood, psychological strain and cognitive effects8,9 reported: - Signifi cantly reduced personal strain, confusion and dejected / depressed moods associated with chronic work stress after 12 weeks of supplementation9

- Signifi cant improvements in scales of mood and stress states and performance trend toward reduced mental fatigue during intense mental processing8

• A meta-analysis (8 trials)10 found that multivitamin/ mineral supplementation for at least 28 days reduced levels of perceived stress, mild psychiatric symptoms, and anxiety

B-COMPLEX VITAMINS

Complementary medicines

| Description |

• Anxiety is a group of conditions characterised by excessive fears and worries that may be diffi cult to control.1 It may be accompanied by other overlapping comorbidities such as depression2

• Stress is a normal human response to a threat, however, when associated with high levels of autonomic arousal, erroneous cognitions, and dysfunctional coping strategies, the effects of stress can signifi cantly impact day-to-day living2

• Around 14% of the Australian population (16–85 years) experience anxiety or stress-related disorders each year2

- 9–12% experience mild disorders3

- Women experience higher rates than men (18% and 11% respectively)2 - The highest rate of anxiety is experienced in the 35–44 y bracket (18%)2

| Management guidelines |

• Psychoeducation (education about the nature of anxiety, its purpose and presentation)2• Psychological treatments2

- Refer patient to psychologist and/or online resource for assessment/treatment2,4

- Cognitive behavioural therapy (CBT) may be at least as effective as medication for many anxiety disorders2

- Online programs may be as effective as face-to- face therapy4

- Mindfulness-based meditation may decrease anxiety with benefi ts still present after 3 years5

• Pharmacological treatments: selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs) and benzodiazepines, however patients tend to prefer CBT and see it as more likely to be effective in the long term2

| NERVOUS SYSTEM | 2

Adverse effects• High doses of vitamin B6 taken over a long period of time may cause peripheral neuropathy.11 This is unlikely to occur at doses <200 mg/d12

Interactions• Folic acid may decrease the activity of phenytoin and methotrexate13

• Folic acid may increase the toxicity of fl uorouracil13

• Ribofl avin (B2) may increase effect of migraine drugs13

Dosage : Recommended dietary intake for adults14

B1mg/d

1.1

B2mg/d

1.1

B3mg/d

14-35

B5mg/d

4-6

B6mg/d

1.3-50

B12ug/d

2.4

Folateug/d

400-1000

Biotinug/d

25

Cholinemg/d

425-3500

KAVA (Piper methysticum)

Mechanism of action• Kava’s key active constituents, the kavalactones, may modulate calcium and sodium channels, modify binding of ligands to GABA receptors, inhibit noradrenaline and dopamine reuptake, and reverse inhibition of monoamine oxidase6,15

ResearchKava may have benefi t in general anxiety disorder (GAD), general anxiety-related disorders, and when tapering off benzodiazepines:6,15

• A 2003 Cochrane review (12 RCTS; n=700) found kava extract had a signifi cant effect in reducing anxiety scores and is an effective symptomatic treatment for anxiety16

• A 2005 meta-analysis (6 RCTs; n=345) found kava extract was effective in patients with non- psychotic anxiety disorders17

• A 2013 RCT (n=75) found an aqueous extract of kava (120/240 mg/d kavalactones) signifi cantly reduced anxiety in patients with GAD. With patients with moderate-severe GAD, the effect size was larger18

• 3 randomised controlled trials have found kava decreases anxiety associated with menopause both for women with concomitant HRT or without19

• There is contradictory evidence for kava being comparable to pharmaceutical antianxiety agents. One clinical trial found kava was as effective as

buspirone in the acute treatment of out-patients suffering from GAD.20 Another trial compared effects of kava and oxazepam on anxiety after a cognitive battery. Kava did not reduce anxiety compared to oxazepam, however, it did not affect cognition whereas oxazepam reduced alertness. The placebo group had an increase in anxiety21

• A randomised controlled trial comparing kava, oxazepam and placebo found a medicinal dose of kava containing 180 mg of kavalactones did not impair driving ability, whereas 30 mg of oxazepam caused some impairment22

Adverse effects• Well tolerated short term

(1–24 weeks)16

• Adverse effects unlikely at recommended dosage19

• Kava has been implicated in several idiosyncratic, rare cases of liver damage. Aqueous extracts are likely to be safer in this context19

• May cause GI upset and headache11

• Not recommended during pregnancy and lactation19

Interactions• Concomitant use with alcohol, barbiturates, benzodiazepines, or other CNS depressants may increase risk of drowsiness and motor refl ex depression11

Dosage• Typically found in tablet/capsule form Dosage range: ~300 mg/d kava extract (providing 105–250 mg kavalactones)11

REFERENCES 1. Mayo-Wilson E, Montgomery P. Media-delivered cognitive behavioural therapy and behavioural therapy (self-help) for anxiety disorders in adults. Cochrane Database of Systematic Reviews 2013; (9):CD005330. 2. Kyrios M, Moulding R, Nedeljkovic M. Anxiety disorders. Assessment and management in clinical practice. Aus Fam Phys 2011; 40(6):370-74. 3. Australian Institute of Health and Welfare. Australia’s health 2014. Australia’s health series no.14. Cat .no. AUS 178. Canberra: AIHW; 2014. 4. Reynolds J, Griffi ths K, Christensen H. Anxiety and depression. Online resources and management tools. Aus Fam Phys 2011; 40(6):382-86. 5. Allen NB, Blashki G, Gullone E. Mindfulness-based psychotherapies: a review of conceptual foundations, empirical evidence and practical considerations. Aust NZ J Psch 2006: 40(4):285-94. 6. Sarris J, Moylan S, Camfi eld DA, et al. Complementary medicine, exercise, meditation, diet, and lifestyle modifi cation for anxiety disorders: a review of current evidence. Evid Based Complement Alternat Med 2012; 2012:809653. 7. Stough C1, Simpson T, Lomas J, et al. Reducing occupational stress with a B-vitamin focussed intervention: a randomized clinical trial: study protocol. Nutr J 2014; 13(1):122. 8. Kennedy D, Veasey R, Watson A, et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacol 2010; 211(1):55-68. 9. Stough C. Scholey A, Lloyd J, et al. The effect of 90 day administration of high dose vitamin B-complex on work stress. Hum Psychopharmacol 2011; 26(7):470-6. 10. Long S, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms and mood in nonclinical samples: a meta-analysis. Psychosom Med 2013; 75(2):144-53. 11. Braun L, Cohen M. Herbs & Natural Supplements. 3rd ed. Chatswood: Elsevier; 2010. 12. Higdon J. An evidence-based approach to vitamins and minerals. Thieme 2003 13. Blackmores Institute 2015. Complementary Medicines Interactions Guide 7th ed. 14. National Health and Medical Research Council (NHMRC). Nutrient Reference Values. http://www.nrv.gov.au. Accessed 18 May 2016. 15. Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J 2010; 9:42. 16. Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev 2003; (1):CD003383. 17. Witte S, Loew D, Gaus W. meta-analaysis of the effi cact of acetonic kava extract WS®1490 in patients with non-psychotic anxiety disorders. Phytother Res 2005;19:183-88 18. Sarris J, Stough C, Bousman CA et al. Kava in the treatment of generalised anxiety disorder: a double-blind, randomised, placebo-controlled study. J Clin Psychopharmacol 2013:33(5):643-8 19. Bone K, Mills S. Principles and Practice of Phytotherapy 2nd ed. Elsevier 2013 20. Boerner RJ, Sommer H, Berger W, et al. Kava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder: an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Phytomedicine 2003; 10 (Suppl 4):38-49 21. Sarris J, Scholey A, Schweitzer I, et al. The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study. Hum Psychopharmacol 2012; 27(3):262-9. 22. Sarris J, Laporte E, Scholey A, King R, Pipingas A, Schweitzer I, Stough C. Does a medicinal dose of kava impair driving? A randomized, placebo-controlled, double-blind study. Traffi c Inj Prev. 2013;14(1):13-7 23. Elsas SM, Rossi DJ, Raber J, et al. Passifl ora incarnata L. (Passionfl ower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method. Phytomedicine 2010; 17(12):940-9. 24. Ulbricht C, Basch E, Boon H, et al. An evidence-based systematic review of passion fl ower (Passifl ora incarnata L.) by the Natural Standard Research Collaboration. J Diet Suppl 2008; 5(3):310-40. 25. Miyasaka LS, Atallah AN, Soares BG. Passifl ora for anxiety disorder. Cochrane Database Syst Rev 2007; (1):CD004518. 26. Su KP, Matsuoka Y, Pae CU.Omega-3 polyunsaturated fatty acids in prevention of mood and anxiety disorders. Clin Psychopharmacol Neurosci 2015; 13(2): 129-37.

Contact education@blackmoresinstitute.org Healthcare Professional Advisory Service 1800 151 493 Website blackmoresinstitute.org

| Diet and lifestyle recommendations |

• Adopt a diet rich in complex carbohydrates, (wholegrains, fruits, vegetables), lean protein and omega-3 rich foods. Decrease refi ned carbohydrates, saturated fats, and processed foods6

• Moderate-graded physical activity may decrease the risk of anxiety6

• Encourage withdrawal of alcohol, caffeine and nicotine which may exacerbate6

• Meditation techniques (mindfulness and other forms of meditation) may reduce anxiety and stress-related symptoms6

| Secondary recommendations |

PASSIONFLOWER (Passifl ora incarnata)

• Preliminary evidence suggests that passionflower may modulate the GABA system and may bind to central benzodiazepine receptors23,24

• Widely used traditionally as a mild sedative and for anxiety and restlessness. Often in combination with other herbs24

− Limited evidence in human trials indicates passionflower may be comparable to oxazepam for reducing anxiety in patients with GAD and may reduce anxiety related to surgery6

• However, a 2009 Cochrane review (2 studies; n=198 ) concluded that despite some positive findings no firm conclusions could be drawn based on insufficient evidence25

• Dosage range: dried herb 0.5–2 g 3–4 times/d11,24

CHAMOMILE (Matricaria recutita)

In the treatment of general anxiety over 8 weeks chamomile showed a modest effect on reducing anxiety relative to placebo6

OMEGA-3 FISH OILS

Supplementation may have regulatory effects on immunomodulation, anti-infl ammation, signal transduction, neurotransmission and neuroprotection, and may reduce and prevent anxiety disorders although data are confl icting26

PASSIONFLOWER (Passifl ora incarnata) CHAMOMILE (Matricaria recutita) (Matricaria recutita)

OMEGA-3 FISH OILS