Nutraceuticals are dietary supplements of naturally occurring substances such as vitamins and minerals. They can be obtained and used without a prescription as they are considered natural health products such as herbal remedies. Nutraceuticals are derived from food sources and are believed to have additional health benefits beyond their basic nutritional value.

Patients with bipolar disorder may be at risk for mood shifts when they are deficient in certain micronutrients [19, 20]. Indeed, screening for vitamin deficiencies such as folic acid, vitamin B12, and vitamin D is part of the standard psychiatric evaluation and treatment of mood disorders. However, much less is known about the relationship between mood and nutritional deficiencies, in part due to inadequate biomarkers for many micronutrients and variation in the individual dietary needs of each patient [20]. There are no studies examining the role of various micronutrients in older age bipolar disorder, but several micronutrients have been studied in adult bipolar disorder and are reviewed here.

St. John’s Wort or Hypericum perforatum is a flowering plant found throughout the world that has been used for medicinal purposes for millennia. Though it has been most extensively studied in the treatment of depression, researchers have been interested in its application to a number of other psychiatric conditions [67]. Unfortunately, there have been no clinical trials to date specifically in bipolar disorder.

Evidence in the depression literature supports use of high-quality, standardized preparations of St. John’s Wort in mild-to-moderate major depression and has been extensively reviewed. There have been dozens of randomized trials, and a recent meta-analysis demonstrated it to be better than placebo and comparable to conventional antidepressants [68]. Hyperforin and hypericin are the active components in St. John’s Wort. It is typically dosed as 900 mg in divided doses two or three times daily, which is equivalent to approximately 1.0 mcg hypericin and 0.5–5 % hyperforin though some may need up to 1800 mg/day for more severe depression [67]. Its mechanisms of action are purported to be wide-based reuptake inhibition of serotonin, dopamine, and norepinephrine as well as MAO-inhibition. It may also have some modulatory effects on GABA and glutamate [69].

There are limited data on St. John’s Wort in older adults. An RCT involving mostly female older adults demonstrated equivalent efficacy of St. John’s Wort (800 mg) compared to fluoxetine (20 mg) with minimal adverse effects [70]. Importantly, cost-effective analysis showed potential economic benefit of St. John’s Wort, with several hundred dollars saved per individual compared to sertraline and venlafaxine [71].

St. John’s Wort is quite tolerable with mild dermatologic reactions and gastrointestinal symptoms as the most commonly reported side effects. In 2010, Kasper and colleagues assessed the tolerability of St. John’s Wort across several randomized control trials compared to paroxetine and other selective serotonin reuptake inhibitors. The authors reported comparable adverse reaction rates for St. John’s Wort to placebo and lower adverse reactions compared to paroxetine and other SSRIs [72]. Treatment with St. John’s Wort carries the risk of inducing mania/hypomania, with multiple cases of St. John’s Wort-induced mania reported in the literature [73, 74]. It is a potent CYP3A4 inducer and a mild inducer of CYP2C9 and CYP1A2 [75]. Psychotropic drugs are metabolized largely by these enzymes, and therefore, their induction can decrease psychotropic drug levels if taken simultaneously. Clinically significant drug interactions include effects on warfarin, cyclosporine, HIV protease inhibitors, theophylline, oral contraceptives, and digoxin. Specifically, St. John’s Wort can reduce warfarin levels via CYP2C9 induction and decrease levels of cyclosporine, HIV protease inhibitors, and oral contraceptives via CYP3A4 induction. St. John’s Wort can reduce the absorption and distribution of digoxin through induction of P-glycoprotein transport protein [76]. It is not recommended to use SSRIs concomitantly with St. John’s Wort given risk of serotonin syndrome and decreasing psychotropic effectiveness due to liver enzyme induction [67].

In summary, there is some evidence to extrapolate from studies conducted in adults with major depression to support the use of St. John’s Wort in older patients with bipolar disorder, particularly in those who cannot tolerate antidepressants. However, it is important to counsel patients that, while tolerable, St. John’s Wort is not without adverse effects. Clinicians should carefully consider possible drug–drug interactions, which could potentially decrease the effectiveness of various medications in the elderly. Moreover, the lack of regulation/standardization by the Food and Drug Administration and potential for variable amounts of active plant product across formulations further increases the potential for adverse consequences from drug–herb interactions. Thus, it may be wise to avoid St. John’s Wort when taking medications with significant drug interactions as described above. Further work is needed to more clearly identify potential use of St. John’s Wort in older adults with bipolar depression, when used in conjunction with mood stabilizers.

Mindfulness meditation and mindfulness-based interventions have grown in popularity, and their clinical benefits have been studied in an array of psychiatric conditions, physical illnesses including pain, and general well-being [77–80]. While the concept of mindfulness originated from Eastern spiritual, and cultural contemplative traditions (e.g., Buddhism), it has also been described in psychological terms as paying attention on purpose to the present moment with nonjudgmental attitude to one’s inner and outer experiences [81]. Both Mindfulness-Based Cognitive Therapy (MBCT) and Mindfulness-Based Stress Reduction (MBSR) were developed by clinical groups to address physical and mental health issues [82–85]. While MBSR has been studied in a number of psychiatric conditions over the years since its inception, there have been several recent studies examining the effectiveness of MBCT in adults with bipolar disorder, though none exclusively in the geriatric population [86–88]. The studies have enrolled mixed ages from 18 to 65 with average age around 40. MBCT combines mindfulness training with cognitive therapy and was initially developed to prevent relapse in major depressive disorder [89]. MBCT has been shown to be more effective in treating residual symptoms of depression and improving quality of life compared to maintenance antidepressant therapy in patients with fully or partially remitted major depressive disorder (MDD) [90]. An open-label, nonrandomized controlled trial comparing MBCT (cohort N = 23) versus sertraline (cohort N = 20) as a first-line treatment for acute major depressive disorder found significant reductions in HAM-D scores but no difference between groups, suggesting MBCT may be a viable alternative to medication for acute depression [91].

A small study of 12 adult patients with bipolar disorder with residual depressive symptoms used a modified version of the MBCT protocol to examine possible changes in mood, attention, and well-being [86]. Although the conditions were not controlled, the authors reported a decrease in depressive symptoms, fewer attention difficulties, an increase in mindfulness, and improvements in emotional regulation, positive effect, and psychological well-being. Subsequent analysis of the same study sample found patient reports of improved executive functioning, memory, and ability to initiate and complete tasks after 3 months of follow-up [92]. Perich and coworkers reported on a small RCT of MBCT + treatment as usual (TAU) versus treatment as usual in bipolar patients (N = 48 MBCT, N = 47 TAU) [88]. The authors reported no benefit of MBCT versus TAU in time to recurrence of mood symptoms or number of recurrences over 12-month follow-up but did demonstrate some improvement in anxiety. However, the study was limited by a short follow-up period relative to previous studies and a high dropout rate in both groups. There is an ongoing 3-prong randomized clinical trial comparing MBCT plus medication management versus an active psycho-education intervention plus medication management versus medication management alone in outpatient bipolar patients with subthreshold depressive symptoms. Results from this study have not yet been published [93].

Mindfulness-Based Cognitive Therapy may exert effects across a broad spectrum of neurocognitive symptoms in bipolar disorder. There is evidence in the literature demonstrating neurocognitive deficits in bipolar patients in various phases of the illness. In particular, patients with bipolar disorder have been found to have impairment in attention, working memory, processing speed, and verbal learning and these neurocognitive deficits contribute to functional impairment even in the euthymic state [94–97]. There is some evidence that MBCT may modulate cognitive processes in these patients. Howell and colleagues completed a pilot EEG study to examine attention control in bipolar patients [98]. Bipolar patients exhibited decreased attention readiness and activation of irrelevant information compared to healthy controls. After an 8-week MBCT course, the patients exhibited improvements in attention readiness and attenuated activation of non-relevant information processing.