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Read the following 3 Video Transcripts: Video Summaries: Mood Stabilizers in the Treatment of Bipolar Disorder: mood stabilizers and bipolar disorder created by Massiah McDaniels Molly Barrett and Paige Hildebrandt this presentation will overview bipolar disorder a typical treatment course for an individual diagnosed with bipolar disorder and with a significant emphasis on pharmacological treatment bipolar disorder includes manic episodes hypomanic episodes and major depressive episodes when distinguishing between bipolar one and bipolar two disorder a clinician must consider whether or not the individual has ever experienced a manic episode at least one occurrence of a manic episode current or past is necessary to meet diagnostic criteria for bipolar one disorder an individual may be diagnosed with bipolar two disorder when they have a current or past history of both hypomanic episodes and depressive episodes in order to qualify for a manic episode an individual displays a change in mood and energy that severely impacts important areas of functioning such as work or social life symptoms must occur all day every day lasting at least one week and have three or more of the following for example an individual with a decreased need for sleep can be seen as a person who only sleeps 2 to 3 hours yet does not feel exhausted or tired similar to a manic episode an individual experiencing a hypomanic episode displays a change in mood and energy that does not severely impact important areas of functioning symptoms must occur all day every day lasting at least four consecutive days and have three or more of the following this stuff builds and it wasn’t like rage but it was pressure and pressure from the the from the mania my head was basically spinning it was racing thoughts and there’s so many thoughts that you can’t see em you just see this whirlwind and you want to be able to reach in and pick and pull out one to be able to look at it but they’re moving so fast you can’t reach in and pull and pick one out and so you have this whirlwind and it’s whirlwind as it goes round much like a tornado creates pressure my ears felt full feel like this pressure is leaking out of my ears and it’s starting to go down to my neck oh my gosh and of course is this scope going on I’m getting more and more anxious I was getting frustrated I’m getting mad I was I’m driving down the street I thought I need I need music because I’ll transfer my energy through music to have it disappear in order to qualify for a major depressive episode an individual shows a change in mood and behavior from previous functioning the individual must have five or more symptoms during a two-week period at least one of the symptoms is depressed mood or loss of interest or pleasure for example an individual with recurrent thoth may have suicidal ideation without a plan a suicide attempt or a specific plan for committing suicide you can imagine that it’s hard to get up out of bed and even go to the supermarket and get your groceries for the day that it can be very difficult to go to work and get all the things that you need to get done either in your work life or again or in your personal life people will report guilt or sometimes feeling like they’re worthless people will also report that they feel like they’re either kind of moving in slow motion which is known as psychomotor retardation and occasionally people will report that they actually feel jittery which is known as psychomotor agitation in addition people will report disturbances in their sleep which are most commonly insomnia so either difficulty falling asleep waking up in the middle of the night or waking up earlier in the morning than one intends to occasionally this can be hypersomnia though where people are sleeping for instance 10 12 13 14 or more hours per day concluded in the following graph as a baseline representing normal functioning a hypomanic episode requires the least amount of time in order to meet the diagnostic criteria a manic episode requires a longer duration than hypomanic episode in addition to increased severity at a time of 7 days the minimum amount of time required for a major depressive episode is the longest of three episodes lasting 14 days hypomanic and manic episodes require above baseline functioning and elevated mood and energy while major depressive episodes fall below baseline of normal functioning but decreased mood and energy this is the etiology of bipolar disorder certain prescriptions and illegal drugs may contribute to bipolar disorder such as Ritalin and other commonly used medications to treat attention deficit disorder can trigger a manic episode impairment and brain functioning may also increase the likelihood of a mood disorder bipolar disorder is also concerned as a family affair according to the DSM there is an average tenfold increased risk among adult relatives of individuals with bipolar one into disorder the hippocampus is the storage house for memories and behavioral inhibition those with the bipolar disorder tend to show a decrease in serotonin which affects the individuals ability to perform memory recall and control behavioral impulses the limbic system is in charge of emotional behavior within the limbic system is the thalamus which relates to emotional regulation evidence has shown that a decrease in the Mew opioid receptors affect the individual’s ability to regulate mood these receptors also play a role in activating rewards systems in the brain in addition to increase in the concentration of stress hormones individuals with bipolar disorder shown imbalance of MU opioid receptors specifically seen during major depressive episodes are abnormalities and reward pathways in the brain there is a decreased release of the neurotransmitter dopamine which is related to pleasure among other functions this would explain why individuals in a major depressive episode experience anhedonia executive function refers to a collection of higher-level psychological processes which allow for the organization of behavior these include working memory inhibitory control and the attentional shifting these processes are associated with the prefrontal cortex the impairment of the executive functioning has been reported during the manic and depressive states of bipolar disorder numerous neurotransmitters have been hypothesized in playing a role in bipolar disorder episodes in this video we will present two neurotransmitters that have been given a large majority of attention in research norepinephrine is a stress hormone that causes muscle contraction when released this neurotransmitter plays a predominant role in our bodies fight-or-flight response when presented with the threatening stimulus increasing in concentration in the synapse between neurons a second neurotransmitter that has been seen to play a significant role in bipolar disorder is serotonin serotonin is a neurotransmitter that plays a role in numerous functions such as sleep appetite sexual activity learning and memory serotonin is also largely linked to mood disorders studies have shown a correlation between low levels of serotonin and depressive symptoms in individuals with bipolar disorder various treatments have been used with individuals diagnosed with bipolar disorder medication has shown to be a popular form of treatment to manage manic and depressive episodes but finding the appropriate medication for each patient can be difficult in the following section we will discuss common pharmacological treatments used in managing bipolar disorder three classes of medication might be used alone or in combination to treat specific episodes of bipolar disorder lithium was approved in the early 1970s by the Food and Drug Administration or FDA for the treatment of mania this choice of drug treatment has shown to be very effective but puts an individual at risk for various side effects anticonvulsants have been prescribed to patients as the solo form of pharmacological treatment or in combination with another medication although this presentation will only discuss depakote lamictal and tegretol as anticonvulsant medications for bipolar disorder other medications may be used such as topamax lyrica and Nerada atypical antipsychotics are not viewed as first-line treatment for mania but can be beneficial for individuals who have less response to other forms of medication in addition to zyprexa abilify simba acts and seroquel other atypical antipsychotics used to treat bipolar disorder include but are not limited to at all and geodon from a collage achill treatment for bipolar disorder berries in the way that these medications affect the central nervous system lithium is believed to mediate the symptoms in both manic and depressive episodes during manic episodes lithium has shown to decrease the amount of norepinephrine in the synapse by enhancing the activity of norepinephrine reuptake into the presynaptic neurons is also theorized that lithium has an effect on levels of serotonin during depressive episodes by increasing levels of tryptophan which is a building block of serotonin there for lithium helps increase levels of serotonin that are deprived during depressive episodes anticonvulsants original purpose was to manage seizure disorder when use on individuals diagnosed with bipolar disorder research has suggested the possibility that these drugs enhance the actions of gaba which is the primary inhibitory neurotransmitter in the central nervous system atypical antipsychotics have shown effectiveness in treating both mania and depression depending on what episode the individual is currently in the choice of which atypical antipsychotic is used differs lithium is noted as the most successful single agent medication for managing bipolar disorder in the 1970s lithium became the first mood stabilizing agent approved by the FDA the Ansah of lithium is non immediate instead patients using lithium do not see changes until 5 to 14 days after initiating lithium drug treatment adherence to medication can be difficult due to the delayed onset for example full stabilization of lithium takes several months some of the most common side effects of lithium include diabetes insipidus excessive urination weight gain nausea vomiting diarrhea and aggravated acne other common side effects of lithium include thirst find hand tremor and an increase in white blood cell count which may lead to leukocytosis the more chronic side effects when using lithium include but are not limited to – I write ism whiter and kidney damage it’s important for patients and family members to be aware of the signs of toxicity due to the small therapeutic window some signs to look out for include lethargy ataxia slurred speech shock and delirium toxicity may also result in coma or death precautions must be taken when including lithium as a choice of pharmacological treatment issues in relation to thyroid and candy function may result from the use of lithium it is important to have both systems checked before beginning treatment using lithium can decrease thyroid production because of this side effect thyroid stimulating hormone levels or TSH levels should be monitored symptoms of hypothyroidism include weight gain fatigue dry skin and intolerance to cold lithium use does not need to be discontinued due to a drop in TSH levels instead TSH can be given to patients experiencing this side effect lithium also affects kidney function because lithium bypasses the liver metabolism it leaves the kidney to be the sole operator in charge of excreting the drug if kidney function decreases there is the possibility that lithium levels will increase in the body due to the inability of the kidney to excrete the drug fast enough which puts the patient at risk for reaching toxic levels another effect that lithium has on the kidney relates to the amount of sodium that is lost during elimination of the drug in this case lithium may remain in the body and lead to toxic levels this is why I’m monitoring both kidney and thyroid functioning is essential when taking lithium for bipolar disorder the amount of lithium administered depends on the stage of treatment varies from one individual to another in general anywhere between 600 to 900 milligrams daily divided into two or more doses is administered when an individual is experienced in acute manic state approximately 1,200 to 2,400 milligrams of lithium are administered once stabilized 600 to 1,800 milligrams per day are given blood levels should be monitored closely following an acute manic state to avoid toxicity it is important to acknowledge the small therapeutic window between the therapeutic dose and toxic level when using lithium it takes approximately 1 to 1.2 Milla equivalents per liter for an individual to see results for lithium unfortunately toxic levels can be anywhere around 1.5 mil equivalents per liter sometimes even lower depakote is a mood stabilizer which typically works for treating rage and instabilities in mood studies have shown it may work quicker than lithium but unfortunately has shown to be ineffective for bipolar depression side effects one may experience our weight gain dizziness and coordination problems lamictal has been approved for acute maintenance for bipolar and to help in the management of rapid cycling lamictal has been shown to be more effective for a depressive phase of mood swings and shown to be effective for mania with lamictal it is important to pay attention to the recommended dosage by slowly increasing the medication over a six-week period side effects for lamictal can include sedation dizziness and in rare cases Steven Johnson syndrome which presents itself as a rash Utah has been considered the second line agent after depakote it has been shown to be used in the management of grand mal seizures yet has been unproven to treat bipolar depression in addition to common side effects of anticonvulsants tegretol may cause a reduction in white blood cell count individuals range anywhere between 600 and 1,200 milligrams per day recommended dosage atypical antipsychotics are not considered first-line agents when treating patients sopressa has been used for the acute and maintenance treatment for bipolar mania similar to zyprexa abilify is also used for the acute and maintenance treatment in bipolar mania simba ex has been used in the treatment of depressive episodes seroquel has been shown to be efficacious and the treatment of bipolar depression common side effects individuals should look for are weight gain and extrapyramidal symptoms a daily dosage of atypical antipsychotics range and must be administered to the patient at the clinicians best judgment atypical antipsychotics share common side effects and differ from patient to patient here we have included a chart that summarizes the purposes of the eight pharmacological treatment options we have discussed thus far as you can see a majority of the drugs discussed in the presentation are effective in managing bipolar mania except for sim by ax and seroquel which instead have shown effectiveness and managing bipolar depression although some medications show improvement and symptoms of both mania and depression such as lithium this chart indicates the main purpose for possible medications used in the treatment of bipolar disorder the following slide contains a helpful mnemonic to remember the different mood stabilizers and how they work inside the brain hopefully this will be a helpful reminder for you later during practice treatment has changed and expanded great deal since I was first diagnosed when I was first diagnosed the only medication drug that was available was lithium and antipsychotic medications like Thorazine but lithium was the first drug that had been found to be really helpful in preventing future episodes feature attacks of of mania and depression in subsequent years there’s been a lot of research done and it’s an absolutely staggering amount of research in terms of understanding the brain and the genetics and the psychological aspects of bipolar illness which is quite wonderful and along the way different classes of drugs have been used drugs that have been used in with seizure disorders the anticonvulsant medications and a depressant medications which can be problematic as some patients with bipolar illness but very helpful and others so there have been many different kinds of medications developed but also there’s been a lot of research on the effectiveness of combining psychotherapy particularly early on in the illness when it’s most difficult for people to accept the idea that they have bipolar and that they will need to be treated for it and psychotherapy can be particularly effective in that group of people it’s often asked particularly when people are young or early and their owners cannot be in psychotherapy alone will that work alone if I have bipolar illness and the answer is rarely very rarely that mostly medication is the central part of treating bipolar almost particularly the more severe forms of bipolar illness so it’s it’s critical to get that across it is a medical condition that requires a medical intervention but can psychotherapy be hugely effective and helpful absolutely because the psychological consequences of having such a you know impairing potentially impairing illnesses but also very painful illness and difficult illness with which to cope in it it affects so many aspects of who you are and how you are your energy your mood your the whole way sly for your relationships your work your ability to concentrate your ability to think so it’s very important to get it diagnosed correctly and get it diagnosed early and to you know reconcile oneself to the idea that you know you’re probably going to be on medication indefinitely but worse things could happen at the beginning of treatment it is essential to administer mood stabilizers to the patient lithium would be the first choice of medication followed by an anticonvulsant and ending with an atypical antipsychotic if neither the former reduced bipolar symptoms lithium is more effective in the treatment of mania but may also be used to manage the symptoms of bipolar depression a combination of medications may also be used although there is no cookie cutter way of combining them benzodiazepines may be combined with other mood stabilizers for the purpose of its sedating effects the combination of lithium and Epico is also a popular option as is shown to increase efficacy of managing bipolar mania when a patient presents with bipolar depression the combination of lithium and an antidepressant is typically used antidepressant medication would never be prescribed as the only form of medication when tree and bipolar depression because of its tendency to switch symptoms from depressive Domanick when a patient presents with bipolar mania the combination of lithium with either a benzodiazepine or antipsychotic may be used choosing which medication will be combined with lithium is dependent on the symptoms the patient is experiencing during the acute phase of treatment is also essential to assess for the risk of suicide due to the fact that bipolar disorder has the highest risk of all psychiatric disorders at 20% when a patient has moved on to the transitional and chronic phase of treatment for bipolar disorder other options of treatment may be used in addition to medication the combination of medication and psychotherapy has shown to be effective in managing the symptoms of manic and depressive episodes psycho therapies focus on the importance of support systems coping mechanisms and working through issues that appear to make life more difficult some of the potential cycle therapies used includes social rhythm therapy interpersonal psychotherapy behavioral therapy cognitive therapy group therapy briefs psychodynamic psychotherapy and marital therapy family involvement has also shown to be essential for both the patient and his or her family families are provided with support as well as education about bipolar disorder in these phases of treatment it cannot be stressed enough for the patient to adhere to medication continuing pharmacological treatment with mood stabilizers is perceived as the most essential component to preventing relapse of manic and depressive episodes Biological Basis of Depression: In this video I’m going to talk about the biological basis of depression. Depression. And I’m not talking about just a passing bad mood but I’m talking about major depressive disorder. Major depressive disorder is a major cause of distress, disability and death from suicide. It is the prototype of the category of mental illnesses called the depressive disorders which involve distress or disability from abnormally negative mood. In addition to negative mood the depressive disorders often involve related symptoms such as feelings of hopelessness or loss of enjoyment in activities. As of 2014 when I’m making this video our understanding of the cause of major depressive disorder is still very limited. When we look at the brains of patients that have major depressive disorder either with the naked eye or with traditional microscope studies there are basically no consistent abnormalities that have been seen in the tissues of these patients. However special scans and research involving animal models have suggested that there are some functional abnormalities that can be detected in the brains of many patients with major depressive disorder. So here in this illustration of the brain we’re looking at the outside of the brain and the different lobes of the cerebrum, the top part of the brain, have been labeled with different colors. And in this illustration we’re also looking at the brain but it’s been divided into right and left halves and we’re looking at the inside of, in this case, the left half of the brain. And a couple of specific areas that have seemed to have abnormal activity in these studies involve this part of the brain in this light blue color which is called the frontal lobe. Let me just write that. Frontal Lobe. A lobe that’s most towards the front of the brain. And over here on the inside that would be all of this stuff, all of this stuff right here is also the frontal lobe. And the other part can’t be seen on the outside it can only be seen on this inside view involves a number of different structures like this structure here and some others that are behind the brain stem over here that are called the limbic structures. Let me just write that word down. The limbic structures. Limbic structures, right here. And these studies have suggested that there appears to be abnormally decreased activity in areas of the frontal lobe and areas of increased activity in areas of the limbic structures. These findings seem to fit well with other studies showing a role for these parts of the brain in regulation of the emotions and in particular, responses to stress. Functions of the brain that seem to be particularly abnormal in patients with major depressive disorder. In regards to stress it’s also been noted that many patients with major depressive disorder have abnormal blood concentrations of certain hormones that are particularly associated with stress. For example the hormone cortisol that’s a major stress hormone. There’s a particular area of the brain that controls most hormones including the stress hormones that’s located right here. And this area is called the hypothalamus. Hypothalamus. And the hypothalamus talks back and forth to many areas of the brain but two areas in particular that it communicates with back and forth are the frontal lobe and the limbic structures of the brain. So it’s thought that perhaps abnormal communication between the frontal lobe and the limbic structure and the hypothalamus in major depressive disorder play a role in why there are these abnormal concentrations of certain hormones related to stress in the blood stream of these patients. These stress hormones may affect most tissues of the body but they also effect the brain itself including the frontal lobes, the limbic structures, and the hypothalamus that actually controls their amounts in the blood in the first place. So for major depressive disorder it’s still unclear which abnormalities of these stress hormones are causes and which are effects of the disease itself. Some features of major depressive disorder also appear to involve abnormalities in neuronal pathways using certain neurotransmitters, the molecules that communicate between neurons in the brain, and the abnormalities of these pathways may cause abnormally decreased or increased activity in certain parts of the brain like the frontal lobes and the limbic structures. Collections of many of these neurons that produce these neurotransmitters have their somas, or their cell bodies, in a few areas of the brain stem, this structure below the cerebrum, and then their axons project to many areas up in the cerebrum, including the frontal lobes and the limbic structures. One of these pathways start in what are called the raphe nuclei of the brain stem. And there are several groups of raphe nuclei at different levels of the brain stem that send projections up to many areas of the cerebrum including the limbic structures and the frontal lobe, and they’re responsible for much of the serotonin that’s secreted in the brain. Serotonin. Which appears to be abnormal in many patients with major depressive disorder. Another pathway starts in an area called the locus coeruleus. Which is located right around here in the brain stem and it also sends long axons up to different areas of the cerebrum and releases a lot of the neurotransmitter called norepinephrine. Norepinephrine. And this also appears to be abnormal in many patients with major depressive disorder. Then there’s a pathway that starts with an area called the ventral tegmental area. Which I’ll just write as VTA for short, which is located around here in the brain stem and which also sends long axons up to different areas of the cerebrum. And the ventral tegmental area supplies much of the dopamine to the brain. Dopamine. These neurotransmitter systems affect the function in many parts of the brain including the frontal lobes and the limbic structures and supporting the idea that abnormalities of these systems are involved in major depressive disorder is the fact that medications that affect these different neurotransmitters dopamine, norepinephrine, and serotonin often improve the symptoms of major depressive disorder. A newer idea that is interesting is that there may be abnormalities of what is called neuroplasticity. Neuroplasticity. Which is a big word that just means that the brain changes in response to experience and these changes may occur down at the level of connection between a couple of brain cells, a couple of neurons in the brain where the strength or efficiency of information flow from one neuron to the next may change based on experience. Or it may happen that the level of networks of neurons that are widespread, different kinds of connections and pathways that informations flowing through the brain based on the experience that the brain is having. And evidence is accumulating that aspects of neuroplasticity appear to be abnormal in animal models of major depressive disorder. But like the other abnormalities that have been found so far it’s unclear if these abnormalities of neuroplasticity are a cause or an effect of major depressive disorder. So there have been a number of biological abnormalities found to go along with the mental abnormalities we see in major depressive disorder. Biological. And other clues to biological factors that may be involves in the cause of major depressive disorder include genetic studies that suggest that a predisposition can be inherited. Several genes related to brain function have been associated with the risk of developing the disease. It may be that these genetic abnormalities increase the risk of the brain developing abnormal responses to negative or stressful events particularly early in life when the brain is still rapidly developing in response to experience but like most if not all mental disorders in addition to the biological factors there does appear to be psychosocial factors as well. Psychosocial factors. Certain psychosocial factors have been linked to the risk of developing major depressive disorder such as childhood abuse, stressful events, or limited social support during adverse circumstances, so that it may be for many, if not most people with major depressive disorders as with most other types of mental illness it seems that an unfortunate constellation of both biological and psychosocial factors combine to cause the illness. Pharmacology – ANTIDEPRESSANTS – SSRIs, SNRIs, TCAs, MAOIs, Lithium ( MADE EASY): in this lecture I’m going to talk about antidepressants so let’s get right into it we all experience changes in mood sometimes we feel happy and energetic and other times we feel sad and irritable fortunately these moods usually don’t last long and we can go about our normal daily routine however life is not always that simple because there are times when we might experience unusually long periods of sadness guilt and decreased interest in activities this is what we call depression sometimes depression can occur alone and other times it is a part of a larger disorder such as bipolar disorder people with bipolar disorder experience periods of depression alternating with periods of mania in which person feels abnormally optimistic euphoric and energetic now treatment of depression and bipolar disorder often involves use of antidepressant drugs which work by elevating levels of certain neurotransmitters in the brain this led to development of monoamine hypothesis which states that depression results from deficiency in one or more of the three key monoamines namely serotonin norepinephrine and dopamine another hypothesis states that this monoamine depletion could also cause the postsynaptic receptors to upregulate thus leading to depression lastly the monoamine hypothesis of gene expression suggests that there might be an abnormal functioning gene that is responsible for causing depression now all that being said keep in mind that these hypotheses are overly simplistic and they don’t accurately explain everything that we observed in research studies however they do give us partial explanation as to why antidepressants work so now let’s switch gears and let’s talk about antidepressant drugs based on their mechanism of action antidepressants can be divided into five different classes number one selective serotonin reuptake inhibitors SSRIs for short number two serotonin norepinephrine reuptake inhibitors SNRIs for short number three tricyclic antidepressants TCAs for short number four monoamine oxidase inhibitors MAOIs for short and lastly number five atypical antidepressants so now before we start discussing each class let me draw some neurons that will help us understand how these antidepressants differ in the way they work so here we have presynaptic serotonergic neuron or in other words serotonin producing neuron and next to it I’m going to draw a presynaptic noradrenergic neuron or in other words norepinephrine producing neuron now these two neurons interact with their postsynaptic counterparts so as you may have already guessed postsynaptic receptors of noradrenergic neuron are beta and alpha-1 while postsynaptic receptors of serotonergic neuron are serotonin often abbreviated as 5-HT receptors now keep in mind that there’s quite a few subtypes of serotonin receptors but for now let’s just keep it simple so going back to our two neurons the serotonin is synthesized from an amino acid tryptophan by serotonergic neurons and it is there stored in vesicles awaiting regulated release on the other side norepinephrine is synthesized from an amino acid tyrosine by noradrenergic neurons and it is also stored there in vesicles awaiting release so now what exactly happens when these neurotransmitters are released well there are a few key things to remember when sero

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