Other Possible Mechanisms Of Lithium For Anxiety
There are numerous other possible mechanisms of action by which lithium may reduce symptoms of anxiety. These mechanisms include: cyclic AMP modulation, epigenetic modification, epinephrine reduction, neuroinflammation downregulation, and oxidative stress reduction. It is also possible that administration of lithium may treat anxiety through the reversal of an underlying lithium deficiency. Understand that some of these mechanisms of lithiums anxiolytic action are currently speculative based on animal data and havent been confirmed in human trials.
Cyclic-AMP modulation: An anxiolytic effect may be generated by lithium partly through modulation of cyclic adenosine monophosphate . Cyclic AMP is a second messenger implicated in many biologic processes and its dysfunction has been linked to anxiety. Many drugs that target cyclic AMP concentrations are effective as anxiolytics.
For example, the drug diazepam has been shown to inhibit PDE cAMP hydrolysis and upregulate cAMP activity plus activation within left frontal regions of the brain. After exposure to stress, rats exhibit alterations in cAMP levels within the amygdala, frontal cortex, hippocampus, and hypothalamus. Whats more, the intensity of various stressors administered to a rat correlates directly with increases in production of cAMP within certain regions of the brain.
Lithium May Provide Answer To Antidepressant Shortcomings
We were unable to process your request. Please try again later. If you continue to have this issue please contact .S. Nassir Ghaemi
NEW ORLEANS In a presentation here, S. Nassir Ghaemi, MD, MPH, of Tufts University School of Medicine, discussed shortcomings of antidepressants, as well as the promise of lithium at low doses for suicide prevention in depression.
There is not much treatment-resistant depression, really, Ghaemi said. Its not that the antidepressants dont work, its that the diagnosis of doesnt work.
He asserted that 25% of treatment-resistant depression is misdiagnosed bipolar depression and 75% is due to the invalidity of the concept of MDD.
In addition, there is strong evidence that antidepressants have a lacking effect on MDD, according to Ghaemi.
Data on antidepressants for MDD
An FDA meta-analysis of all maintenance randomized controlled trials on antidepressants for MDD indicated a mean relapse rate difference of 18% compared with placebo.
Antidepressants resulted in a 52% reduction in relapse vs. placebo, and 94% of relapses occurred after 2 weeks post-randomization.
According to Ghaemi, these findings indicated no real clinical benefit of antidepressants for MDD, as they only worked half of the time and can cause significant side effects.
Further, pharmaceutical studies may be misleading regarding antidepressant efficacy.
More effective treatment options
More maintenance data is needed.
Your Hormones And Your Mood
Of course, there are also other factors other than personality that increases your risk of having mood disorders. More than personality, your hormones play a very vital role in your overall physiological and psychological health. Hormonal imbalances, such as having low testosterone and high estrogen have been seen to cause depression and anxiety in men, quite similar to effects of estrogen imbalance in women which is often evident during menses and menopause.
With this, its important to keep your hormones in check and maintain a state of balance in your body. Anabolic Health specializes in mens hormonal health, while Women in Balance specializes in womens hormonal health. You can visit these websites to find out more about hormones and the things you can do to maintain or restore hormonal balance to keep your body at optimum health.
The following posts are some of the most popular trending posts over at Anabolic Health:
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Lithium Mechanisms And Predictors Of Response
How can a simple ion have such robust and diverse effects? Lithium is a medal ion Li+ whose radius is close to that of sodium Na+ and many of its actions resemble those of calcium Ca++. Although it was initially thought that an understanding of lithiums mechanism of action would reveal the neuropathology underlying bipolar disorder, the panoply of its proposed actions has precluded this proposition. At the same time, the fact that lithium is such a dirty drug with a multiplicity of actions may be important to its diverse therapeutic effects, as the sheer numbers of its actions may lead to the reregulation of multiple pathways and abnormalities in bipolar disorder .
It is of interest that lithium appears to work best in those with: classical presentations of bipolar disorder a positive family history of a mood or bipolar disorder euphoric, rather than dysphoric, mania and discrete episodes and clear well intervals. It works less well in those with rapid cycling or multiple episodes before starting treatment, and in those with an anxiety or substance comorbidity, or mood incongruent delusions . Those with a sequence of depressionmaniawell interval respond less well than those with a pattern of MDI . Several biochemical predictors of response have been reported, and confirmation of these is eagerly awaited.
What Type Of Lithium Supplements Are Available
There are three types of over-the-counter lithium supplements:
Ionic lithium: is a liquid form that contains lithium chloride. This form can be especially helpful for children or patients who are sensitive to treatment, as it is easy to start at a low dose and build up to a therapeutic dose. Typically, ionic lithium is prescribed at 0.5 – 1mg.
Plant-based lithium: is a unique form of lithium made from vegetables that are grown in high-dose lithium soil. Currently, there is only one manufacturer who produces plant-based lithium. This form may be better absorbed and utilized, as our bodies are used to digesting lithium in plants. In my practice, some of the best reports and feedback come from patients with depression who use plant-based lithium.
Lithium orotate: is a salt with orotate, a naturally-occurring substance in the body. Patients taking lithium orotate experience far fewer side-effects compared to lithium medication. This may simply be because lithium orotate is prescribed at much lower doses than the medication. Others have argued that it can enter cells where it is needed, resulting in less toxicity to other organs.
Because lithium orotate does not have well-designed, large-scale studies to support its use for bipolar disorder, it is not recommended as an alternative for those currently on lithium carbonate medication.
Spectrum of lithium intake in humans. Graph is not drawn to scale, and values are based on numerical averages, not a general consensus.
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Cyclic Amp Secondary Messengers
Lithium’s therapeutic effects are thought to be partially attributable to its interactions with several signal transduction mechanisms. The cyclic AMP secondary messenger system is shown to be modulated by lithium. Lithium was found to increase the basal levels of cyclic AMP but impair receptor coupled stimulation of cyclic AMP production. It is hypothesized that the dual effects of lithium are due to the inhibition of G-proteins that mediate cyclic AMP production. Over a long period of lithium treatment, cyclic AMP and adenylate cyclase levels are further changed by gene transcription factors.
Lithium Side Effects: Often More Benign Than Presumed
Contrary to conventional belief, lithiums side-effect profile at usual therapeutic doses is relatively benign. Moreover, if side effects such as tremor do occur at usual therapeutic levels, doses can be reduced to below ones side-effect threshold, especially as many of lithiums clinical effects can be seen at lower levels .
Although lithium can lower thyroid hormone levels, increase TRH, and induce hypothyroidism in 15% of individuals, this is easily corrected by thyroid hormone supplementation.
Although lithium can cause nephrogenic diabetes insipidus because of its block of antidiuretic effects , these can be moderated by amiloride and potentially by the carbonic anhydrase inhibitor acetazolamide . On a positive note, lithium can prevent or reverse the hyponatremia induced by carbamazepine . Lithium via its effects on colony-stimulating factor can reverse the benign white cell suppression of carbamazepine mediated by its inhibition of CSF.
Lithium can be associated with increases in serum calcium, sometimes related to the induction of secondary hyperparathyroidism by an adenoma. This can be worked up by measurement of parathyroid hormone, imaging of the parathyroid glands, and treated by surgery . Lithium-induced tremor can be treated with dose reduction and -blockers .
Lithium can cause a variety of skin lesions, most often acne and psoriasis. These are often amenable to treatment, but in severe cases drug discontinuation may be required .
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Lithium In Treatment Of Mania
While manic episodes are often the most impressive part of BD, their duration is usually shorter compared to that of other disease phases in both BD-I and BD-II. A number of pharmacological agents have been investigated and have proven their efficacy in the treatment of mania, including lithium . The network meta-analysis by Cipriani et al. found an effect size of 0.40 SMD, indicating a moderately sized effect, which is comparable to other anti-manic agents . For example, lithium showed a comparable efficacy to quetiapine in a 12-week RCT . Despite its proven anti-manic properties, lithium has lost some of its relevance in the treatment of mania in the recent years, partly due to the large number of SGAs that have been licensed for this indication. Reasons for favoring SGAs over lithium include the shorter time of dosage increase and sedation, a common side effect of SGAs that is often welcomed during manic agitation. Further potential disadvantages of lithium include the small therapeutic window and hence the necessity for repeated serum level controls . In addition, no parenteral application is available for lithium. Notwithstanding these limitations, lithium should be considered as a first-line therapy for manic episodes, as long-term phase-prophylactic treatment is almost always required afterward, for which lithium is considered the first choice. In the treatment of manic episodes, higher levels of 0.8 to 1.2 mmol/L are required in order to achieve optimal response.
Lithium Orotate Benefits Vs Other Forms Of Lithium
With these positive things about lithium, you may wonder why it still has a cloudy reputation until today. This is because in very high doses, the mineral can be toxic to the body. The body poorly absorbs pharmaceutical forms of lithium lithium carbonate and lithium citrate hence theyre always taken in huge doses to obtain a satisfactory effect. Individuals taking these versions have to be monitored and have their blood checked regularly to ensure that they do not reach toxic levels.
Lithium orotate anxiety treatment differs from prescription lithium. The orotate binder transports the lithium easily into the membranes of the cells, requiring a much lower dosage than prescription forms of lithium. For example, severe cases of depression may only require a dose of 150 mg of lithium orotate per day. This is far lower than 900 to 1800 mg of prescription lithium. Because intake is generally lower, there are no adverse side effects, making it safe for every day use.
We recommend this lithium orotate supplement for daily use to help balance moods.
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What Drugs Are Used To Treat Depression
Atypical depression goes to least twice more probable to influence ladies than guys. In addition, atypical depression tends to start at an earlier age and also depression dosage lithium unipolar last longer than typical depression. Benazzi F. Screening DSM IV interpretation of atypical depression. Lam RW, Stewart JN. The validity of atypical depression in DSM IV. Posternak MA, Zimmerman M. Effects of atypical depression.
Relevant info for this testimonial was recognized via a multistep literary works search of PubMed using the terms bipolar depression/bipolar problem plus other relevant terms. This type of bipolar affective disorder incorporates hypomanic and also depressive signs and symptoms that last for 2 weeks. Yet, in this problem, neither the hypomanic nor depressive signs fulfill the scientific requirements for a manic or depressive episode. Antidepressant monotherapy is contraindicated in bipolar depressive episodes since depression dosage lithium unipolar antidepressants can cause fast biking or changes into mania/hypomania. Its likewise been suggested that the older term lugs a stigma in pop culture and that both manic and depression are now utilized to define everyday feelings as well as emotions. As a result, bipolar affective disorder is now the favored term and the one that health care experts utilize in diagnosis.
Verdict: Lithium May Help A Subset Of Individuals With Anxiety Disorders
Upon review of the available literature, it seems as though lithium has likely never undergone any randomized controlled trials for the treatment of anxiety disorders. There are likely many reasons lithium has never been tested as an anxiolytic, including: requirement of frequent serum monitoring, unwanted side effects, adverse long-term effects, and lack of preexisting data indicating that it could be an effective anxiolytic. That said, there is some evidence from a 1986 case report to suggest that lithium may prove useful for the management of refractory panic disorder.
In this case report by Cournoyer, it was reported that a 40-year-old patient had been treated with clomipramine for depression experienced unremitting panic disorder. Adjuvant lithium administration effectively treated the panic. Other than this lone case report, there are animal model data indicating that lithium reduces anxiety-like behavior in fear-conditioned rats.
It may be worth noting that there are anecdotal reports circulating throughout the internet suggesting that lithium is effective for the alleviation of anxiety. Though anecdotal reports do not qualify as legitimate scientific data, they support the hypothesis that lithium could reduce anxiety in a subset of the population. Nonetheless, with new anxiety medications in the pipeline and the abundance of safe and effective currently-available anxiolytics, lithium may never be properly evaluated for the treatment of anxiety.
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Side Effects Of Lithium Over The Lifespan
Lithium treatment is associated with a number of undesired side-effects that involve different organ systems. Gastro-intestinal complaints such as nausea, vomiting, and diarrhoea are relatively common. Nausea affects around 1020% of patients, particularly in the early phase of treatment and often diminishes with longer treatment duration . Fine hand tremor is reported by about 25% of patients treated with lithium , the absolute risk increase was 9.6% compared to placebo in short-term trials . Clinically, it presents as postural tremor and its frequency and intensity correlate with lithium serum levels . Management mainly includes dose reduction. Pharmacological management with propranolol is recommended only in cases of severe tremor, as beta-blockers may introduce other side-effects .
The risk of hypothyroidism is increased 5.78-fold compared to placebo and lithium may lead to increased blood calcium and parathyroid hormone levels . TSH and calcium levels should therefore be monitored regularly hypothyroidism can be managed by levothyroxine substitution and is no reason for discontinuing lithium.
Cardiological harms may also arise from lithium treatment. In a recent review, the most common ECG abnormality was T wave inversion. Further alterations include QT prolongation and ventricular tachyarrhythmias .
The Course Of Unipolar Depression
Unipolar depression in its classic form is an episodic disorder with a high persisting morbidity. The first episode starts commonly around 42 years of age and can last for a period of up to 12 months or more. The episode will then remit and the patient can be symptom free for a period of several years before it is followed by a further episode in a substantial proportion of patients. Many patients will have multiple episodes the length of an episode usually does not vary but the interval between the episodes decreases. After 3 or 4 episodes, patients can spend a considerable proportion of their lives with a depressive episode . . The population attributable risk for suicide in mood disorders is 26% for males and 32% for females . In clinical populations and by 18 months, 10% of individuals with unipolar depression attempt suicide when ill particularly among patients with previous attempts, female patients, those with poor social support, and those aged 40 years or less , Similar rates were observed over 5 years in primary care . The incidence of suicide attempts during major depressive episodes was 21-fold and fourfold during partial remission compared with full remission .
A retrospective study of phenomenology and treatment course of delusional depression reported a high relapse rate of unipolar DD . It was proposed that unipolar DD will require long-term maintenance pharmacologic treatment, as 40.7% of the relapses occurred during or shortly after a medication taper.
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Lithium In Treatment Of Bipolar Depression
Bipolar depression is the predominant pole in BD type I and type II and responsible for a large number of suicides. The suicide rate is 20-times above that of the general-population , which is considerably larger than that of unipolar depression . Bipolar depression is also associated with a high rate of morbidity and mortality due to comorbid somatic disorders . However, treatment of bipolar depression is challenging for clinicians, as the classical treatment strategies of unipolar depression show small, if any, effects . The lack of effectiveness of antidepressants in BD has been the topic of an ongoing controversy . There is evidence that antidepressants may worsen the course of the disease in patients with mixed symptoms or RC by increasing the switch risk or causing tachyphylaxis after repeated antidepressant drug exposures .
Isnt Lithium Only Prescribed For Bipolar Disorder Can It Help Depression Or Other Conditions
In addition to bipolar disorder, preliminary evidence shows that those struggling with the following challenges may benefit from lithium supplementation:
Suicidal ideation and impulsivity
Anxiety including panic attacks
Most notably, low-dose lithium seems to have a strong potential to help those suffering from depression.
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Does Our Body Need It
Yes, but it’s not that important. There are no known diseases that you acquire from lack of lithium, for example. So, having low lithium levels does not seem to be immediately harmful.
However, it does seem to increase the risk of suicide, committing crimes and drug use. Therefore, it is likely that it has some effect on our brain chemistry.
How Lithium May Treat Anxiety Disorders
There are numerous mechanisms by which lithium may prove useful as an intervention for anxiety disorders. Potential anxiolytic mechanisms of lithiums action include: serotonergic modulation , downregulation of norepinephrine, inhibition of GSK-3 enzymes, and inositol modulation. As of current, it is unclear as to which mechanisms are chiefly responsible for the induction of an anxiolytic effect following administration of lithium.
It is possible that a specific mechanism such as upregulation of extracellular serotonin is the single most important anxiolytic mechanism of lithiums action. On the other hand, its also possible that all mechanisms of lithiums action contribute to an anxiolytic effect reported by certain users. That said, since not all individuals with anxiety disorders exhibit the same underlying neurobiological expressions , its fair to speculate that the most substantial anxiolytic mechanisms of lithiums action may be subject to individual variation.
Serotonergic modulation: The chief mechanism by which lithium may reduce symptoms of anxiety is through modulation of the serotonin system. As most know, there are strong associations between serotonin system abnormalities and anxiety disorders. Specifically, anxiety disorders are linked to irregular: extracellular serotonin levels, 5-HT receptor activity, 5-HT receptor density, serotonin synthesis, metabolism and reuptake, as well as serotonin turnover within specific areas of the brain.
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