The depression which occurs in the context of bipolar disorder may have a variety of unique features (sometimes such a depression may occur BEFORE a clear manic episode has ever happened, so a depression with these features can sometimes be a warning sign of latent bipolarity, or a risk sign that bipolar disorder may develop in the future):
1) excessive sleep (rather than insomnia), along with marked physical lethargy
2) depression beginning early in life (during teenage or young adult years)
3) depressive episodes of short duration
4) depressive episodes having psychotic features (e.g. delusions)
5) other "atypical" depressive features, such as increased eating
6) Sometimes a very rapid response to antidepressants (e.g. within one or two doses)
Nevertheless, these features are not invariably present in bipolar depression; and many people may have depressive episodes with these features, who do not have bipolar disorder.
Conversely, in my opinion, there is one significant element from a person's history which points strongly away from a diagnosis of bipolar depression:
If a person has taken an antidepressant, especially at a high dose, and especially for a long period of time (over 3 months), and especially a tricyclic antidepressant or venlafaxine -- if a person has taken such an antidepressant on its own, without a mood stabilizer, and WITHOUT developing overt symptoms of mania, this is fairly strong evidence against underlying bipolarity.
Some of the recent evidence about treating bipolar depression leads us to question the role, value, or safety of antidepressants in the bipolar population.
http://www.ncbi.nlm.nih.gov/pubmed/18727689
(a 2008 review, showing little effect of antidepressants when added to mood stabilizers in treating bipolar disorder over at least 6 months of follow-up)
http://www.ncbi.nlm.nih.gov/pubmed/17392295
(this is from the New England Journal of Medicine--one of the world's leading medical journals--in 2007, and it showed, over 26 weeks of follow-up, that adding antidepressants to a mood stabilizer regime did not improve outcome, in fact the antidepressant group did not do quite as well)
Which treatments have an evidence base in bipolar depression?
1) Lamotrigine. It has the advantage of helping modestly with depressive symptoms with a low risk of causing mania. It may be true that some of the studies over the past few years have exaggerated the benefit of lamotrigine, however. In any case, it appears quite safe, and can be helpful for some people. There is a small risk of a very serious skin rash with this drug, otherwise it is quite safe and well-tolerated.
http://www.ncbi.nlm.nih.gov/pubmed/19200421
(a recent study looking at Lithium + Lamotrigine vs. Lithium + Placebo over 8 weeks of follow-up; the benefits of lamotrigine are significant but modest)
http://www.ncbi.nlm.nih.gov/pubmed/15003074
(this study also showed a benefit from lamotrigine, over a whole year, but there was no placebo group, so the results carry much less weight)
2) Other mood stabilizers, e.g. lithium, valproate, and carbamazepine. Unfortunately these drugs are probably more effective for preventing manic episodes than for preventing or treating depression. Yet, the combination of a standard mood stabilizer with another agent such as lamotrigine could be a valid step.
3) Atypical antipsychotics, e.g. olanzapine, quetiapine, and risperidone. These drugs undoubtedly are beneficial as mood stabilizers, possibly more so than the standard mood stabilizers such as lithium or valproate. There is evidence that antipsychotics + other mood stabilizers are additively effective in combination. They can be worth a try for treating bipolar depression. Unfortunately, if the bipolar depression is already characterized by excessive sleep, tiredness, and appetite, antipsychotics can sometimes make these symptoms worse. But if there are psychotic features with the depression, an antipsychotic can be an essential part of the treatment.
4) Omega-3 supplements : see my previous post
5) Light therapy: I have seen this be helpful at times. The light exposure may need to be carefully titrated (e.g. just a few minutes at a time), to prevent overstimulation or agitation. Light therapy requires the purchase of a 10 000 Lux light box, which could cost about $200-300.
http://www.ncbi.nlm.nih.gov/pubmed/18076544
6) Cognitive-behavioural therapy. Elements of CBT help with most anything, it seems to me (from learning to play the violin, to doing mathematics, to treating anxiety or depression from any cause). CBT can be adapted so as to be more tolerable and interesting (some of the workbooks can be hard to get through). I think its core features require daily written work, journaling, conducting a dialog with oneself about thoughts and emotions (hopefully to work at identifying forms of depressive thinking, and being willing to challenge such thoughts if they occur), and deliberately challenging oneself behaviourally to face fears, a little at a time. In bipolar disorder CBT may work best in conjunction with ideas that help to stabilize or structure daily behavioural rhythms (e.g. getting up regularly in the morning, having a routine, eating regularly, exercising, doing some intellectually challenging work, doing some creative work, going to bed around the same time, etc.). Of course, in depression of any sort, it can be extremely hard to initiate or maintain such lifestyle habits--if there is too much fatigue or lack of motivation to get started with very much, I encourage getting started with the very smallest of tasks or daily structures, and building from there; consistency is more important than amount.
http://www.ncbi.nlm.nih.gov/pubmed/18324665
7) Other psychotherapy: basic supportive care can be very important, provided there is a resilient, trusting therapeutic relationship
8) Antidepressants: despite the negative results of late, there are selected individuals for whom antidepressants may be very helpful. Over the past decade, bupropion has perhaps been the first antidepressant to consider, due to its lower rate of causing a manic switch, and possibly its higher likelihood of helping with the low energy states characteristic of bipolar depression. SSRI antidepressants have been the second-choice agents. MAOI's are probably lower risk with respect to causing manic switch, and the reversible MAOI moclobemide could be a good option. Venlafaxine and tricyclic antidepressants have been agents to avoid, due to their high risk of causing a manic switch.
References:
http://www.ncbi.nlm.nih.gov/pubmed/16449476
http://www.ncbi.nlm.nih.gov/pubmed/16880481
9) Stimulants: I have found that stimulants can be quite useful in bipolar depression, provided that they are not increasing psychotic symptoms or agitation. They have the advantage of working quickly, helping immediately with energy and attention, and often helping with mood. Furthermore, they can be withdrawn quickly if manic symptoms or agitation arises; if stimulants are withdrawn quickly, it causes a relative state of sedation. (Note that there is some evidence from a few older studies that stimulant treatment can actually reduce symptoms of mania) There are several older stimulants, such as methylphenidate (Ritalin), and dextroamphetamine (Dexedrine), and several newer formulations of these older drugs (e.g. Adderall). A newer, atypical stimulant called modafinil can be an option as well. However, modafinil is quite expensive and often not covered by medication plans in Canada.
References:
http://www.ncbi.nlm.nih.gov/pubmed/15383134
http://www.ncbi.nlm.nih.gov/pubmed/18980736
http://www.ncbi.nlm.nih.gov/pubmed/16974196
http://www.ncbi.nlm.nih.gov/pubmed/367183
http://www.ncbi.nlm.nih.gov/pubmed/3312177
(the above two references are to older, interesting studies showing that stimulant treatments actually helped REDUCE manic symptoms acutely--I cite this as evidence that stimulants are reasonable to use in bipolar patients, however I would not go so far as to recommend stimulants in the treatment of mania, as other anti-manic treatments are much more effective and accepted as a standard of care)
10) ECT:electroconvulsive therapy is unequivocally effective for treating both depression and mania. However, there may be a higher risk of mild but persistent cognitive side-effects in the bipolar population:
http://www.ncbi.nlm.nih.gov/pubmed/17653292
If there are "borderline" phenomena occuring in the context of bipolar depression, once again some of Dawson's ideas may be helpful (see my previous postings about borderline personality); these involve emphasizing the role and competence of the individual patient in choosing treatment options, and avoiding an authoritarian stance on the part of the therapist.
Other references:
http://www.ncbi.nlm.nih.gov/pubmed/18992784
(A recent study correlating early age of onset for depression with bipolarity, severity, recurrence, etc.)
http://www.ncbi.nlm.nih.gov/pubmed/18199233
(A review of diagnostic issues regarding bipolar depression)
Tuesday, February 10, 2009
Probabilistic Model of Psychotropic Medication Effects
This is an idea I have considered for many years. It fits with my overall view of a lot of evidence from treatment studies.
For many actions in life, an event either happens, or it doesn't. This seems obvious, I guess. You either throw a ball, or you don't. You either show up for work, or you don't. (Mind you, in my own case, I would say that my own modest level of athletic skill causes me quite often to "sort of" throw a ball, or "sort of" swim.)
In medicine, many actions are similarly unambiguous. The surgical removal of an appendix either happens, or it doesn't. An infection either responds to an antibiotic, or it doesn't. Clear.
Yet, I find that many treatments in medicine are much less clear.
In the case of psychiatric treatments, it has been a theory of mine that the drug (or therapy) may reduce the probability of a symptom occurring, in addition to, or instead of, directly reducing the symptom (or not). This phenomenon may be apparent not only in studies of populations, but in an individual.
Many disease processes are driven by multiple variables, which, together, alter probabilities of symptom recurrence. The variables may include genetic factors, environmental stress, etc. There may be a core phenomenon in nature, as manifest on a chemical, or even quantum-mechanical, level, of minute, truly random events, influencing a cascade of effects. The presence of a medication in the body may be just one more variable, influencing the likelihood of a symptom occuring, or developing, or advancing.
Some medications may appear not to be working, if a short-term view is taken. But in a longer-term view, it may be seen that symptom frequency and intensity is diminished. This is consistent with the theory that the medication affects probabilities.
This theory supports the idea that medications, and other psychiatric treatments, could have an important preventative role, beyond their role in an acute situation. And it encourages giving treatments a long period of time to work--at least months, if not years-- in order to most accurately assess effectiveness.
There have been some long-term studies which support this idea, but unfortunately most of the treatment studies in psychiatry have been relatively short-term (only a few months of follow-up, rarely more than a year).
For many actions in life, an event either happens, or it doesn't. This seems obvious, I guess. You either throw a ball, or you don't. You either show up for work, or you don't. (Mind you, in my own case, I would say that my own modest level of athletic skill causes me quite often to "sort of" throw a ball, or "sort of" swim.)
In medicine, many actions are similarly unambiguous. The surgical removal of an appendix either happens, or it doesn't. An infection either responds to an antibiotic, or it doesn't. Clear.
Yet, I find that many treatments in medicine are much less clear.
In the case of psychiatric treatments, it has been a theory of mine that the drug (or therapy) may reduce the probability of a symptom occurring, in addition to, or instead of, directly reducing the symptom (or not). This phenomenon may be apparent not only in studies of populations, but in an individual.
Many disease processes are driven by multiple variables, which, together, alter probabilities of symptom recurrence. The variables may include genetic factors, environmental stress, etc. There may be a core phenomenon in nature, as manifest on a chemical, or even quantum-mechanical, level, of minute, truly random events, influencing a cascade of effects. The presence of a medication in the body may be just one more variable, influencing the likelihood of a symptom occuring, or developing, or advancing.
Some medications may appear not to be working, if a short-term view is taken. But in a longer-term view, it may be seen that symptom frequency and intensity is diminished. This is consistent with the theory that the medication affects probabilities.
This theory supports the idea that medications, and other psychiatric treatments, could have an important preventative role, beyond their role in an acute situation. And it encourages giving treatments a long period of time to work--at least months, if not years-- in order to most accurately assess effectiveness.
There have been some long-term studies which support this idea, but unfortunately most of the treatment studies in psychiatry have been relatively short-term (only a few months of follow-up, rarely more than a year).
Omega-3 Supplementation
Omega-3 fatty acids are present in a variety of foods.
The fatty acids EPA and DHA are present mainly in fish such as salmon, herring, mackerel, anchovies, and sardines. These fatty acids, especially DHA, are probably important for brain function, and are also found in the retina of the eye.
Another omega-3 fatty acid, ALA, is present from plant sources such as canola oil, flax, and walnuts. ALA may be converted in the body to DHA.
There is some evidence that there are health benefits from diets higher in omega-3 fatty acids, or diets supplemented with extra omega-3.
Of interest for psychiatry, omega-3 supplementation may be a safe adjunct in the treatment of depression. Fish oil is probably the simplest source of extra EPA and DHA.
The only problem with increasing fish consumption is the exposure to environmental contaminants such as mercury and PCBs. Fish oil capsules may actually have less of these contaminants than pure fish, especially if the oil has been refined to remove contaminants. In any case, I think the benefit-risk ratio is very favourable, and that 1-3 capsules per day of fish oil is quite safe. And I feel confident to recommend increased fish intake in the diet. For vegetarians, increased intake of walnuts, canola, and flax could be recommended.
http://www.ncbi.nlm.nih.gov/pubmed/18183532
(a review of the studies over the past decade looking at omega-3 supplements in mood disorders)
http://www.ncbi.nlm.nih.gov/pubmed/16741195
(a nice review from The American Journal of Psychiatry in 2006, summarizing epidemiological data associating low fish consumption with higher rates of mood disorder, and summarizing some of the treatment studies showing antidepressant effects of omega-3 supplements in depression, bipolar disorder, and borderline personality)
http://www.ncbi.nlm.nih.gov/pubmed/19156158
(this is a recent study showing beneficial effects of omega-3 supplements in children with bipolar symptoms;but it was not a randomized or controlled study)
http://www.ncbi.nlm.nih.gov/pubmed/19200125
(this is a recent local study analyzing fish oil supplements for environmental pollutant levels, such as PCBs. Based on this study, one should avoid supplements of products such as seal or shark oils, which have much higher contaminant levels.)
http://www.ncbi.nlm.nih.gov/pubmed/19139352
(one of the articles summarizing evidence that omega-3 intake reduces the incidence or progression of macular degeneration, which is a common cause of visual loss in those over 65 years of age).
http://www.ncbi.nlm.nih.gov/pubmed/19064523
(a huge study, published in 2006, involving data from over
40 000 people over 18 years of follow-up--it shows a slight reduction in cardiac disease associated with higher fish consumption, but no change in overall "major chronic disease risk". But, incredibly, and unfortunately, they did not include mood or other psychiatric disorders in their assessment of "chronic disease" outcomes. Yet, studies of this type exemplify that The American Journal of Clinical Nutrition is an excellent journal, a valuable and practical source of evidence-based health information which could guide nutritional choices).
The fatty acids EPA and DHA are present mainly in fish such as salmon, herring, mackerel, anchovies, and sardines. These fatty acids, especially DHA, are probably important for brain function, and are also found in the retina of the eye.
Another omega-3 fatty acid, ALA, is present from plant sources such as canola oil, flax, and walnuts. ALA may be converted in the body to DHA.
There is some evidence that there are health benefits from diets higher in omega-3 fatty acids, or diets supplemented with extra omega-3.
Of interest for psychiatry, omega-3 supplementation may be a safe adjunct in the treatment of depression. Fish oil is probably the simplest source of extra EPA and DHA.
The only problem with increasing fish consumption is the exposure to environmental contaminants such as mercury and PCBs. Fish oil capsules may actually have less of these contaminants than pure fish, especially if the oil has been refined to remove contaminants. In any case, I think the benefit-risk ratio is very favourable, and that 1-3 capsules per day of fish oil is quite safe. And I feel confident to recommend increased fish intake in the diet. For vegetarians, increased intake of walnuts, canola, and flax could be recommended.
http://www.ncbi.nlm.nih.gov/pubmed/18183532
(a review of the studies over the past decade looking at omega-3 supplements in mood disorders)
http://www.ncbi.nlm.nih.gov/pubmed/16741195
(a nice review from The American Journal of Psychiatry in 2006, summarizing epidemiological data associating low fish consumption with higher rates of mood disorder, and summarizing some of the treatment studies showing antidepressant effects of omega-3 supplements in depression, bipolar disorder, and borderline personality)
http://www.ncbi.nlm.nih.gov/pubmed/19156158
(this is a recent study showing beneficial effects of omega-3 supplements in children with bipolar symptoms;but it was not a randomized or controlled study)
http://www.ncbi.nlm.nih.gov/pubmed/19200125
(this is a recent local study analyzing fish oil supplements for environmental pollutant levels, such as PCBs. Based on this study, one should avoid supplements of products such as seal or shark oils, which have much higher contaminant levels.)
http://www.ncbi.nlm.nih.gov/pubmed/19139352
(one of the articles summarizing evidence that omega-3 intake reduces the incidence or progression of macular degeneration, which is a common cause of visual loss in those over 65 years of age).
http://www.ncbi.nlm.nih.gov/pubmed/19064523
(a huge study, published in 2006, involving data from over
40 000 people over 18 years of follow-up--it shows a slight reduction in cardiac disease associated with higher fish consumption, but no change in overall "major chronic disease risk". But, incredibly, and unfortunately, they did not include mood or other psychiatric disorders in their assessment of "chronic disease" outcomes. Yet, studies of this type exemplify that The American Journal of Clinical Nutrition is an excellent journal, a valuable and practical source of evidence-based health information which could guide nutritional choices).
Monday, February 9, 2009
Lithium
I'd like to develop this post gradually, as there is a lot of evidence to summarize and refer to.
But here is a start:
"Mood stabilizers" are drugs which are thought to help treat the symptoms of bipolar disorder. It is hoped that these drugs might reduce manic symptoms, prevent recurrence of manic symptoms, while also reducing or preventing symptoms of depression.
The first treatments for manic episodes were sedatives, including barbiturates and antipsychotics.
The first "mood stabilizer" though, was lithium carbonate.
Lithium itself is the third-simplest element in the universe, after hydrogen and helium. It tends to form salts. It is structurally very similar to sodium, which is a salt-forming element essential to most every life function (that is why we find sodium ions abundantly in all body fluids, and in a similar concentration in the ocean; table salt consists of sodium and chlorine atoms which join together as crystals). Yet, lithium is not normally present in the human body, and is much less common in the universe as well, compared to hydrogen, oxygen, carbon, sodium, etc.
The mechanism of lithium's action in the body, when used as a drug, is still poorly understood. Its similarity to sodium is probably essential to its mechanism. I'll add to this commentary later, but for now I will say that the mechanism of lithium salts probably involves multiple actions inside of nerve cells; these actions may modulate cellular activity.
Here are some of the clinical actions of lithium carbonate, when used as a medication in those with bipolar disorder (I will list the actions in order of how clearly proven and substantial the effect is):
1) It reduces symptoms of mania
2) It may reduce the length of a manic episode (note that just because a treatment reduces symptom severity, it may not reduce the duration of the symptoms).
3) It may prevent the recurrence of manic symptoms
4) It may prevent the recurrence of depressive symptoms
5) It may reduce depressive symptoms when they occur
There are other uses for lithium carbonate as well:
1) It can be combined with an antidepressant to improve symptom control in unipolar depression
2) It may help treat specific symptoms such as irritability and rage
3) It helps prevent cluster headaches (a type of severe, recurrent headache)
Lithium is probably most useful in "classic bipolar disorder", in which individuals experience manic episodes with elevated mood (as opposed to irritable or "dysphoric" mood), and in which the mood episodes are not recurring frequently during an average year (i.e. there is no "rapid cycling").
Here are some of the side-effects of lithium:
1) thirst, increased urine production
2) tremor (shaky hands)
3) nausea
4) sedation -- usually it is a much less pronounced type of sedation compared to antipsychotics, benzodiazepines, or other "sleeping pills". But there can be feelings of reduced energy, reduced clarity of thinking, or lethargy
5) toxicity to the kidneys -- this is not common, but needs to be checked for regularly
6) inhibition of thyroid function -- this is not permanent, nor is it harmful to the thyroid gland (in fact, it may "rest" the thyroid gland); but diminished thyroid levels, if present, requires treatment with a thyroid supplement)
7) acne or other skin rashes
8) toxicity in overdose
There have been a few studies questioning the effectiveness of lithium, particularly in terms of its value in preventing recurrent mood episodes. But for many people it does appear to be very effective, both as an acute treatment and as a preventative agent. It probably works much better as an "anti-manic" agent than an "anti-depressant".
There are various forms of lithium, and various dosing regimes. In most cases, it can be dosed simply: once at bedtime. The concentration of lithium in the blood needs to be measured periodically. Levels which are too high can increase the likelihood of toxicity (mind you, excessive levels could usually be assessed on the basis of side-effect complaints); levels which are too low may not be effective.
In my experience, some people may benefit from staying on lithium, but adjusting the dose to a point that is more tolerable for them. It may not necessarily be true that everyone needs to have a full therapeutic concentration of lithium in order for it to work. For some people, the side effects may outweigh the benefit at full doses.
However, it is a frequent situation in an emergency room, or on a mood disorders hospital ward, that people with clear histories of bipolar disorder, stable on medication, end up having a recurrence of severe mania a few weeks or months after tapering or stopping their medication (often lithium). In some of these cases, the manic symptoms may have already been building up, leading the person to discontinue their medication (rather than the other way around). But in many of these cases, it seems to me that the lithium had been protecting them, and that the recurrence of mania happened because of medication discontinuation.
There is also some evidence that sudden lithium discontinuation can provoke increased mood instability. So, while there are no overt withdrawal symptoms from stopping lithium, it should be tapered slowly if possible (I would say over 1-2 months at least).
It should be emphasized that lithium is not a perfect drug, either in terms of side effects or in terms of effectiveness. Many people on full doses of lithium still experience relapses of mania. But it is quite clear, from decades of experience, that lithium can be helpful for many people with bipolar disorder.
References:
http://www.ncbi.nlm.nih.gov/pubmed/17547586
(a 2007 Cochrane review of mood stabilizers, showing good evidence for lithium, but also encouraging use of other mood stabilizers--which for some people could be superior to lithium-- such as valproate and atypical antipsychotics)
http://www.ncbi.nlm.nih.gov/pubmed/8120960
(a 1994 JAMA article showing the effectiveness of lithium and valproate, compared to placebo, in acute mania)
http://www.ncbi.nlm.nih.gov/pubmed/10807488
(a negative study, comparing lithium, valproate, and placebo; published in the major journal Archives of General Psychiatry in 2000--it shows very little difference between lithium, valproate, and placebo treatments with respect to relapses in bipolar patients over a 1-year period; however this study was probably biased in favour of high placebo effects and lower medication treatment effects, for a variety of reasons)
http://www.ncbi.nlm.nih.gov/pubmed/10891035
(a randomized, placebo-controlled study from Archives of General Psychiatry in 2000, showing a pronounced effect of lithium in reducing aggression in hospitalized children with conduct disorder)
http://www.ncbi.nlm.nih.gov/pubmed/16924942
http://www.ncbi.nlm.nih.gov/pubmed/3314489
(a Dutch review article from 2006, and an older article from a U.S. nephrology journal, summarizing the risk of kidney disease associated with lithium; about 15-20% of people taking lithium long-term may experience a decline in kidney function. While this decline is usually mild, I think that an alternative mood stabilizer should be strongly considered if someone is developing signs of reduced kidney function while on lithium).
But here is a start:
"Mood stabilizers" are drugs which are thought to help treat the symptoms of bipolar disorder. It is hoped that these drugs might reduce manic symptoms, prevent recurrence of manic symptoms, while also reducing or preventing symptoms of depression.
The first treatments for manic episodes were sedatives, including barbiturates and antipsychotics.
The first "mood stabilizer" though, was lithium carbonate.
Lithium itself is the third-simplest element in the universe, after hydrogen and helium. It tends to form salts. It is structurally very similar to sodium, which is a salt-forming element essential to most every life function (that is why we find sodium ions abundantly in all body fluids, and in a similar concentration in the ocean; table salt consists of sodium and chlorine atoms which join together as crystals). Yet, lithium is not normally present in the human body, and is much less common in the universe as well, compared to hydrogen, oxygen, carbon, sodium, etc.
The mechanism of lithium's action in the body, when used as a drug, is still poorly understood. Its similarity to sodium is probably essential to its mechanism. I'll add to this commentary later, but for now I will say that the mechanism of lithium salts probably involves multiple actions inside of nerve cells; these actions may modulate cellular activity.
Here are some of the clinical actions of lithium carbonate, when used as a medication in those with bipolar disorder (I will list the actions in order of how clearly proven and substantial the effect is):
1) It reduces symptoms of mania
2) It may reduce the length of a manic episode (note that just because a treatment reduces symptom severity, it may not reduce the duration of the symptoms).
3) It may prevent the recurrence of manic symptoms
4) It may prevent the recurrence of depressive symptoms
5) It may reduce depressive symptoms when they occur
There are other uses for lithium carbonate as well:
1) It can be combined with an antidepressant to improve symptom control in unipolar depression
2) It may help treat specific symptoms such as irritability and rage
3) It helps prevent cluster headaches (a type of severe, recurrent headache)
Lithium is probably most useful in "classic bipolar disorder", in which individuals experience manic episodes with elevated mood (as opposed to irritable or "dysphoric" mood), and in which the mood episodes are not recurring frequently during an average year (i.e. there is no "rapid cycling").
Here are some of the side-effects of lithium:
1) thirst, increased urine production
2) tremor (shaky hands)
3) nausea
4) sedation -- usually it is a much less pronounced type of sedation compared to antipsychotics, benzodiazepines, or other "sleeping pills". But there can be feelings of reduced energy, reduced clarity of thinking, or lethargy
5) toxicity to the kidneys -- this is not common, but needs to be checked for regularly
6) inhibition of thyroid function -- this is not permanent, nor is it harmful to the thyroid gland (in fact, it may "rest" the thyroid gland); but diminished thyroid levels, if present, requires treatment with a thyroid supplement)
7) acne or other skin rashes
8) toxicity in overdose
There have been a few studies questioning the effectiveness of lithium, particularly in terms of its value in preventing recurrent mood episodes. But for many people it does appear to be very effective, both as an acute treatment and as a preventative agent. It probably works much better as an "anti-manic" agent than an "anti-depressant".
There are various forms of lithium, and various dosing regimes. In most cases, it can be dosed simply: once at bedtime. The concentration of lithium in the blood needs to be measured periodically. Levels which are too high can increase the likelihood of toxicity (mind you, excessive levels could usually be assessed on the basis of side-effect complaints); levels which are too low may not be effective.
In my experience, some people may benefit from staying on lithium, but adjusting the dose to a point that is more tolerable for them. It may not necessarily be true that everyone needs to have a full therapeutic concentration of lithium in order for it to work. For some people, the side effects may outweigh the benefit at full doses.
However, it is a frequent situation in an emergency room, or on a mood disorders hospital ward, that people with clear histories of bipolar disorder, stable on medication, end up having a recurrence of severe mania a few weeks or months after tapering or stopping their medication (often lithium). In some of these cases, the manic symptoms may have already been building up, leading the person to discontinue their medication (rather than the other way around). But in many of these cases, it seems to me that the lithium had been protecting them, and that the recurrence of mania happened because of medication discontinuation.
There is also some evidence that sudden lithium discontinuation can provoke increased mood instability. So, while there are no overt withdrawal symptoms from stopping lithium, it should be tapered slowly if possible (I would say over 1-2 months at least).
It should be emphasized that lithium is not a perfect drug, either in terms of side effects or in terms of effectiveness. Many people on full doses of lithium still experience relapses of mania. But it is quite clear, from decades of experience, that lithium can be helpful for many people with bipolar disorder.
References:
http://www.ncbi.nlm.nih.gov/pubmed/17547586
(a 2007 Cochrane review of mood stabilizers, showing good evidence for lithium, but also encouraging use of other mood stabilizers--which for some people could be superior to lithium-- such as valproate and atypical antipsychotics)
http://www.ncbi.nlm.nih.gov/pubmed/8120960
(a 1994 JAMA article showing the effectiveness of lithium and valproate, compared to placebo, in acute mania)
http://www.ncbi.nlm.nih.gov/pubmed/10807488
(a negative study, comparing lithium, valproate, and placebo; published in the major journal Archives of General Psychiatry in 2000--it shows very little difference between lithium, valproate, and placebo treatments with respect to relapses in bipolar patients over a 1-year period; however this study was probably biased in favour of high placebo effects and lower medication treatment effects, for a variety of reasons)
http://www.ncbi.nlm.nih.gov/pubmed/10891035
(a randomized, placebo-controlled study from Archives of General Psychiatry in 2000, showing a pronounced effect of lithium in reducing aggression in hospitalized children with conduct disorder)
http://www.ncbi.nlm.nih.gov/pubmed/16924942
http://www.ncbi.nlm.nih.gov/pubmed/3314489
(a Dutch review article from 2006, and an older article from a U.S. nephrology journal, summarizing the risk of kidney disease associated with lithium; about 15-20% of people taking lithium long-term may experience a decline in kidney function. While this decline is usually mild, I think that an alternative mood stabilizer should be strongly considered if someone is developing signs of reduced kidney function while on lithium).
Noise Pollution
Peace and quiet are important for mental and physical health.
Here are a few links to references:
http://www.ncbi.nlm.nih.gov/pubmed/14757721
http://www.ncbi.nlm.nih.gov/pubmed/15936421
(A 2005 study published in Lancet which showed that noise causes increased irritability, and a negative impact on cognitive development in school-aged children)
On a related note, the use of music players such as iPods can cause permanent hearing loss, particularly if people have the volume turned up very high. People are more likely to use higher iPod volumes if the background noise level is also high. Here are some links to information and evidence:
http://www.hearinglossweb.com/Medical/Causes/nihl/mus/ipod/ipod.htm#fast
http://www.ncbi.nlm.nih.gov/pubmed/19124629
http://www.ncbi.nlm.nih.gov/pubmed/17430434
http://www.ncbi.nlm.nih.gov/pubmed/17711774
Also, the sound volume at a rock concert or a nightclub is sufficient to cause hearing damage, especially if this is an activity done regularly without hearing protection. I recommend using earplugs at rock concerts (yes, I'm serious!) Here is some evidence:
http://www.ncbi.nlm.nih.gov/pubmed/8499785
http://www.ncbi.nlm.nih.gov/pubmed/16825883
http://www.ncbi.nlm.nih.gov/pubmed/12176760
Here are a few links to references:
http://www.ncbi.nlm.nih.gov/pubmed/14757721
http://www.ncbi.nlm.nih.gov/pubmed/15936421
(A 2005 study published in Lancet which showed that noise causes increased irritability, and a negative impact on cognitive development in school-aged children)
On a related note, the use of music players such as iPods can cause permanent hearing loss, particularly if people have the volume turned up very high. People are more likely to use higher iPod volumes if the background noise level is also high. Here are some links to information and evidence:
http://www.hearinglossweb.com/Medical/Causes/nihl/mus/ipod/ipod.htm#fast
http://www.ncbi.nlm.nih.gov/pubmed/19124629
http://www.ncbi.nlm.nih.gov/pubmed/17430434
http://www.ncbi.nlm.nih.gov/pubmed/17711774
Also, the sound volume at a rock concert or a nightclub is sufficient to cause hearing damage, especially if this is an activity done regularly without hearing protection. I recommend using earplugs at rock concerts (yes, I'm serious!) Here is some evidence:
http://www.ncbi.nlm.nih.gov/pubmed/8499785
http://www.ncbi.nlm.nih.gov/pubmed/16825883
http://www.ncbi.nlm.nih.gov/pubmed/12176760
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