Researchers are constantly looking for new, faster-acting, more effective antidepressants with fewer side-effects. And one new antidepressant in particular is starting to look pretty promising. It's called agomelatine (brand name Valdoxan) and it isn't quite like any other antidepressant on the market, because it doesn't affect the uptake of serotonin, noradrenaline or dopamine.
Agomelatine is a specific agonist of MT1 and MT2 melatonin, and to some extent it is also an antagonist at serotonin 5HT-2C receptors (as are SSRIs). Melatonin is a hormone produced by the pineal gland, which has an important role in the sleep-wake cycle ('circadian rhythm'). Abnormalities in circadian rhythms are highly prevalent in mood disorders, including depression, so agomelatine has many potential advantages for treating depression, because it may help regulate the sleep-wake cycle. This means it helps you sleep better, without sedating you and causing daytime sleepiness. Which is a big deal, considering many SSRI's and SNRI's cause insomnia, and therefore make sleeping problems worse.
But the really big thing which makes agomelatine exciting is the lack of side effects. Unlike SSRI's and SNRI's, it does not cause weight gain, sexual dysfunction or withdrawal symptoms. It has no discontinuation syndrome. That is a big deal. Weight gain and sexual side-effects are the two main complaints people seem to have about SSRI's, and it's a big reason some people stop taking them. And trying to come of an SSRI can really suck. Not to mention how bad the discontinuation can get for venlafaxine.
As with any new antidepressant, its efficiacy is questionable. It has, however, demonstrated superior efficacy to sertraline in one study, and fluoxetine in another. In other studies, it had a higher efficiacy than placebo, especially for treating severe depression, and a lower rate of relapse. As with many antidepressants, some studies showed no difference between agomelatine and placebo. It's worth noting that those studies also showed no difference between the active controls (paroxetine and sertraline) and placebo.
If agomelatine really works, with such a good level of tolerability, it's definitely a very exciting step forward in antidepressant treatment. It was released in the UK in July this year, so watch this space.
Thursday, 8 October 2009
Sunday, 4 October 2009
Antidepressants: 10 Things You Need To Know
1. What Antidepressants Are
Antidepressants are drugs which are used to treat clinical depression, although many of them are approved for use in other conditions as well. There are five main types:
2. How We Think They Work
It's not known for certain how antidepressants work, but most of them are thought to work by inhibiting the reabsorption of certain chemicals in the brain. For those of you who know nothing about the brain, let me run you through a couple of basics. The brain is made up of about 10 billion brain cells, or 'neurons'. Each one connects to about 10,000 others, but they don't actually touch one another. They are separated by small gaps called synapses. This is my fantastic diagram of two brain cells:
Brain cells communicate with each other by releasing chemicals called neurotransmitters, which other brain cells respond to. These chemicals are then either broken down or re-absorbed, because otherwise your neurons would be soaking in chemicals all the time, and they wouldn't be able to respond to other neurons any more. The most common antidepressants slow down the reabsorption of certain neurotransmitters, so that your neurons get longer to respond to them. That is why they are called 're-uptake inhibitors'. The three main neurotransmitters involved in depression are thought to be serotonin, noradrenaline and dopamine. SSRI's work on serotonin, NRI's work on noradrenaline, Multiple Reuptake Inhibitors work on two or more of the three and Tricyclics work on all three.
MAOI's work a bit differently; they slow down a chemical called Monoamine Oxidase, which breaks down neurotransmitters. The effect, however, is the same. Your brain cells get to soak in the right chemicals for longer.
3. Not Everyone Needs Medication
Antidepressants should not be used for treating mild depression for two reasons:
Severe depression is different. If you're so depressed that you spend hours lying in bed trying to get up the strength to get up and make a cup of tea, it's pretty pointless for somebody to tell you that you need to get some exercise. That's the kind of depression where you need medication straight away.
4. They Don't Work Straight Away
Some people respond almost immediately to antidepressants, but others may not notice any difference for up to a month after they start taking, or six weeks for fluoxetine (Prozac). If there's still no response after about six to eight weeks, that's when it's time to try a different drug.
5. Side-Effects
Common side-effects when you start an antidepressant are: dry mouth, nausea, headaches, sleepiness or insomnia, weight gain and constipation or diarrhoea. These effects are usually temporary and they should pass in a few weeks. SSRI's can make you anxious at first and they can sometimes cause longer-term problems with weight gain and with your sex drive. Tricyclics can affect your blood pressure, and MAOI's can have serious and potentially fatal interactions with certain types of foods. If you are prescribed an MAOI, your doctor will tell you which foods to avoid. Always read the patient information leaflet for the full list of side-effects before you take an antidepressant.
6. Suicide Risk
All antidepressants carry an increased risk of suicide. Therefore it's very important that anybody who is starting an antidepressant is carefully monitored by a doctor, and that they report any suicidal thoughts immediately. It's a good idea to keep a list of phone numbers you can call in a crisis, and this should include your doctor or therapist or a crisis team. The risk of suicide associated with antidepressants is a lot higher in children and teenagers.
7. Alcohol
Generally speaking, it's best to avoid alcohol if you're taking an antidepressant. A few drinks here and there or a glass of wine with your meal is usually okay, but some combinations should not be mixed with alcohol at all. Ever. So ask your doctor first. Large amounts of alcohol also tend to make you more depressed, which can further increase your risk of suicide in the first few weeks of treatment.
8. Physical Dependency
When you've been taking an antidepressant for a while, your brain gets used to the chemical changes the meds cause. Although antidepressants aren't addictive in the true sense of the word, some people experience withdrawal symptoms when they stop taking their medication especially if it's an SSRI, and even more so if you stop taking them abruptly. Withdrawal from reuptake inhibitors can cause severe fatigue, headaches, nausea, vomiting, chills, dizziness, shaking or tremors, insomnia, electric-shock like sensations, vertigo, confusion and suicidal thoughts, plus "brain shivers". These symptoms are collectively known as SSRI Discontinuation Syndrome, but multiple reuptake inhibitors which affect serotonin can also cause this. Don't try to come off your medication on your own. You need to gradually reduce your dose over time to avoid withdrawal effects. Also, some drugs leave the body very quickly so even if you only miss one dose you can experience withdrawal symptoms. It's important to take your meds at the same time every day (or however often your psychiatrist or pharmacist told you to). Getting a pill organiser is a good idea.
9. Sometimes They Stop Working
SSRI's and other reuptake inhibitors can work really well at first and then suddenly stop working. It's known as the 'poop-out' effect. I kid you not, that's what doctors call it. It usually just means you need to switch to another medication in the same class, so don't panic if you find your medication suddenly stops working. Luckily, if you take a break from an antidepressant then start taking it again, it will often work as well as it did when you took it the first time. So if you find two SSRI's that work well for you, but they tend to quit working after a while, you can cycle between the two of them for as long as you need to.
10. Antidepressants Are Not A Cure
For people with severe depression, medication can be a very important part of treatment. It can be the difference between being completely incapacitated, and being able to engage in therapy, being able to go for a walk etc. But antidepressants aren't a magic cure. They don't suddenly make everything okay. Severe mental illness can't be fixed overnight. It usually takes months or even years of treatment to reach some sort of stability where you can get back to your life as it was before you became ill. And non-drug treatments are just as important for people who take medication as they are for those who don't. Doctors, patients, friends, family etc often expect medication to make the problem go away straight away. Some people will even wonder why you can't just "snap out of it" already. It doesn't work like that. Recovering from a serious depressive illness is like recovering from major surgery. It takes time, and the right treatment.
Just a reminder: I'm not a doctor and this is not a replacement for proper medical advice. You should always consult the patient information leaflet for a medication before taking it.
Antidepressants are drugs which are used to treat clinical depression, although many of them are approved for use in other conditions as well. There are five main types:
- Tricyclic Antidepressants (TCAs)
- Selective Serotonin Re-uptake Inhibitors (SSRIs)
- Noradenaline Re-uptake Inhibitors (NRIs)
- Multiple Re-uptake Inhibitors
- Monoamine Oxidase Inhibitors (MAOIs)
2. How We Think They Work
It's not known for certain how antidepressants work, but most of them are thought to work by inhibiting the reabsorption of certain chemicals in the brain. For those of you who know nothing about the brain, let me run you through a couple of basics. The brain is made up of about 10 billion brain cells, or 'neurons'. Each one connects to about 10,000 others, but they don't actually touch one another. They are separated by small gaps called synapses. This is my fantastic diagram of two brain cells:
Brain cells communicate with each other by releasing chemicals called neurotransmitters, which other brain cells respond to. These chemicals are then either broken down or re-absorbed, because otherwise your neurons would be soaking in chemicals all the time, and they wouldn't be able to respond to other neurons any more. The most common antidepressants slow down the reabsorption of certain neurotransmitters, so that your neurons get longer to respond to them. That is why they are called 're-uptake inhibitors'. The three main neurotransmitters involved in depression are thought to be serotonin, noradrenaline and dopamine. SSRI's work on serotonin, NRI's work on noradrenaline, Multiple Reuptake Inhibitors work on two or more of the three and Tricyclics work on all three.
MAOI's work a bit differently; they slow down a chemical called Monoamine Oxidase, which breaks down neurotransmitters. The effect, however, is the same. Your brain cells get to soak in the right chemicals for longer.
3. Not Everyone Needs Medication
Antidepressants should not be used for treating mild depression for two reasons:
- Recent research shows that if you're not severely depressed, antidepressants don't work any better than placebos.
- While the placebo effect can be useful, antidepressants have risks and side-effects, so for those with mild to moderate depression, the risks basically outweigh any potential benefits.
Severe depression is different. If you're so depressed that you spend hours lying in bed trying to get up the strength to get up and make a cup of tea, it's pretty pointless for somebody to tell you that you need to get some exercise. That's the kind of depression where you need medication straight away.
4. They Don't Work Straight Away
Some people respond almost immediately to antidepressants, but others may not notice any difference for up to a month after they start taking, or six weeks for fluoxetine (Prozac). If there's still no response after about six to eight weeks, that's when it's time to try a different drug.
5. Side-Effects
Common side-effects when you start an antidepressant are: dry mouth, nausea, headaches, sleepiness or insomnia, weight gain and constipation or diarrhoea. These effects are usually temporary and they should pass in a few weeks. SSRI's can make you anxious at first and they can sometimes cause longer-term problems with weight gain and with your sex drive. Tricyclics can affect your blood pressure, and MAOI's can have serious and potentially fatal interactions with certain types of foods. If you are prescribed an MAOI, your doctor will tell you which foods to avoid. Always read the patient information leaflet for the full list of side-effects before you take an antidepressant.
6. Suicide Risk
All antidepressants carry an increased risk of suicide. Therefore it's very important that anybody who is starting an antidepressant is carefully monitored by a doctor, and that they report any suicidal thoughts immediately. It's a good idea to keep a list of phone numbers you can call in a crisis, and this should include your doctor or therapist or a crisis team. The risk of suicide associated with antidepressants is a lot higher in children and teenagers.
7. Alcohol
Generally speaking, it's best to avoid alcohol if you're taking an antidepressant. A few drinks here and there or a glass of wine with your meal is usually okay, but some combinations should not be mixed with alcohol at all. Ever. So ask your doctor first. Large amounts of alcohol also tend to make you more depressed, which can further increase your risk of suicide in the first few weeks of treatment.
8. Physical Dependency
When you've been taking an antidepressant for a while, your brain gets used to the chemical changes the meds cause. Although antidepressants aren't addictive in the true sense of the word, some people experience withdrawal symptoms when they stop taking their medication especially if it's an SSRI, and even more so if you stop taking them abruptly. Withdrawal from reuptake inhibitors can cause severe fatigue, headaches, nausea, vomiting, chills, dizziness, shaking or tremors, insomnia, electric-shock like sensations, vertigo, confusion and suicidal thoughts, plus "brain shivers". These symptoms are collectively known as SSRI Discontinuation Syndrome, but multiple reuptake inhibitors which affect serotonin can also cause this. Don't try to come off your medication on your own. You need to gradually reduce your dose over time to avoid withdrawal effects. Also, some drugs leave the body very quickly so even if you only miss one dose you can experience withdrawal symptoms. It's important to take your meds at the same time every day (or however often your psychiatrist or pharmacist told you to). Getting a pill organiser is a good idea.
9. Sometimes They Stop Working
SSRI's and other reuptake inhibitors can work really well at first and then suddenly stop working. It's known as the 'poop-out' effect. I kid you not, that's what doctors call it. It usually just means you need to switch to another medication in the same class, so don't panic if you find your medication suddenly stops working. Luckily, if you take a break from an antidepressant then start taking it again, it will often work as well as it did when you took it the first time. So if you find two SSRI's that work well for you, but they tend to quit working after a while, you can cycle between the two of them for as long as you need to.
10. Antidepressants Are Not A Cure
For people with severe depression, medication can be a very important part of treatment. It can be the difference between being completely incapacitated, and being able to engage in therapy, being able to go for a walk etc. But antidepressants aren't a magic cure. They don't suddenly make everything okay. Severe mental illness can't be fixed overnight. It usually takes months or even years of treatment to reach some sort of stability where you can get back to your life as it was before you became ill. And non-drug treatments are just as important for people who take medication as they are for those who don't. Doctors, patients, friends, family etc often expect medication to make the problem go away straight away. Some people will even wonder why you can't just "snap out of it" already. It doesn't work like that. Recovering from a serious depressive illness is like recovering from major surgery. It takes time, and the right treatment.
Just a reminder: I'm not a doctor and this is not a replacement for proper medical advice. You should always consult the patient information leaflet for a medication before taking it.
Friday, 25 September 2009
Thursday, 24 September 2009
The Physiology of Depression
The physiology of mood disorders is complicated, and not particularly well understood. What we do know comes from brain imaging and looking at the levels of different chemicals in the brain. There may be some long, confusing words you've never heard of here, but stick with it, because what this stuff tells us is important.
In unipolar depression, the physical problem is believed to be an imbalance of either serotonin, noradrenaline or dopamine in the brain; or two or all three of those. Exactly how we don't know, and the exact imbalance is probably different for everybody, but generally speaking, most people with depression have less serotonin, or noradrenaline in their brain than healthy people do. The pathophysiology of Bipolar Disorder is poorly understood, but it is probably linked to the same three neurotransmitters as well as some structural abnormalities in the amygdala, basal ganglia and prefrontal cortex.1
PET (Positron Emission Topography) and SPECT (Single Proton Emission Computed Topography) scans are two types of brain scans which show how active or inactive the different areas of the brain are. PET scans of depressed brains compared to normal ones show a significant reduction in overall brain activity. This is why everything seems ten times harder when you're depressed and why it's much harder to concentrate and remember things. People with depression are like cars running on half a tank of gas, or in some cases hardly any gas at all. You can barely get out of the driveway, let alone make it around the block. In other words, if you're depressed, you can't expect yourself to carry on with your normal life while you are ill. So give yourself a break!
In people with Bipolar Disorder, PET and SPECT imaging usually shows decreased activity in the prefrontal cortex, which is involved in emotion and planning, the amygdala, which is associated with mood regulation, and the hippocampus2. This may explain the intense highs and lows bipolar sufferers experience. Patients in the depressed phased of a cycle show very similar scan results to patients with unipolar depression. In the manic phase, imaging shows both left-right and dorso-ventral asymmetry in the basal temporal cortex. I have absolutely no idea what that means.
But whether you have any idea of what a basal temporal cortex is or not, the important thing to understand is that...
Sources:
1. Internet Mental Health
2. Rachel Pollock, PhD & Irving Kuo, MD - "Neuroimaging in Bipolar Disorder"
3. Jerod Poore, Crazy Meds
4. Karl Hempel, MD - "Depression: What You Need To Know"
5. Amen Clinics SPECT Imaging
In unipolar depression, the physical problem is believed to be an imbalance of either serotonin, noradrenaline or dopamine in the brain; or two or all three of those. Exactly how we don't know, and the exact imbalance is probably different for everybody, but generally speaking, most people with depression have less serotonin, or noradrenaline in their brain than healthy people do. The pathophysiology of Bipolar Disorder is poorly understood, but it is probably linked to the same three neurotransmitters as well as some structural abnormalities in the amygdala, basal ganglia and prefrontal cortex.1
PET (Positron Emission Topography) and SPECT (Single Proton Emission Computed Topography) scans are two types of brain scans which show how active or inactive the different areas of the brain are. PET scans of depressed brains compared to normal ones show a significant reduction in overall brain activity. This is why everything seems ten times harder when you're depressed and why it's much harder to concentrate and remember things. People with depression are like cars running on half a tank of gas, or in some cases hardly any gas at all. You can barely get out of the driveway, let alone make it around the block. In other words, if you're depressed, you can't expect yourself to carry on with your normal life while you are ill. So give yourself a break!
In people with Bipolar Disorder, PET and SPECT imaging usually shows decreased activity in the prefrontal cortex, which is involved in emotion and planning, the amygdala, which is associated with mood regulation, and the hippocampus2. This may explain the intense highs and lows bipolar sufferers experience. Patients in the depressed phased of a cycle show very similar scan results to patients with unipolar depression. In the manic phase, imaging shows both left-right and dorso-ventral asymmetry in the basal temporal cortex. I have absolutely no idea what that means.
But whether you have any idea of what a basal temporal cortex is or not, the important thing to understand is that...
[in serious mental illness] Your brain is physically injured, and like any other part of the body that has received a physical injury, it needs the proper care to heal... The problem that far too many people have is that they can't see the injury, therefore it is not a real injury... - Jerod Poore, Crazy Meds 3Whether you suffer from a mood disorder or not, you should know that they are genuine medical conditions with physical manifestations in the brain. Just because you can't see the physical problem, it doesn't mean that it's not there. If you could have one of those fancy brain scans yourself, you would see it. Use this information to accept the fact that you're ill, and you need rest and medical treatment. You're not weak or selfish or any of the other things people may accuse you of. You're not well. Got it? Good.
Sources:
1. Internet Mental Health
2. Rachel Pollock, PhD & Irving Kuo, MD - "Neuroimaging in Bipolar Disorder"
3. Jerod Poore, Crazy Meds
4. Karl Hempel, MD - "Depression: What You Need To Know"
5. Amen Clinics SPECT Imaging
Subscribe to:
Posts (Atom)