In case you missed my psych meds 101 series, here’s the post on antidepressants.
In case you missed my psych meds 101 series, here’s the post on antidepressants.
Wouldn’t it be nice if the treatment of depression was simple? Unfortunately, there’s nothing simple about depression treatment in the real world Treatment resistant depression (TRD) refers to illness that hasn’t respond to trials of adequate duration and dosage of at least two antidepressants. The STAR*D research study found that only about 1/3 of people get well with one anti-depressant trial, a further 1/4 get well with a second trial, and only 67% get well after a fourth medication trail. That’s a whole lot of people not getting well. So if you fall into that category of TRD, what are your options?
If depression isn’t responding to treatment, it’s important that the diagnosis be re-evaluated. Could this be bipolar depression? In that case, the treatment strategy may need to be quite different, and antidepressants alone are seldom effective for bipolar depression. Is there a medication, medical condition (e.g. hypothyroidism), or substance use that could be contributing to the problem that needs to be addressed in order to properly treat the depression? Is there unaddressed trauma that needs to be targeted?
Let’s say the diagnosis is major depressive disorder and no complicating factors can be identified. Has psychotherapy been tried? If not, that’s always a great place to start. Other first steps might be to increase dose, switch antidepressants, or try antidepressant combos. Another strategy is augmentation, which refers to medications that are added onto an antidepressant regimen to achieve a greater therapeutic effect. Options include lithium, thyroid hormone, antipsychotics, and stimulants.
Ok, so what if you’ve tried, maxed out, and failed on these various treatment strategies? Ketamine, a dissociative anaesthetic, has a novel mechanism of action, affecting the glutamate system in the brain. It is a relatively new treatment and availability can be limited, but there is some good research supporting its effectiveness.
There are a number of other drugs that have been studied that are potential options although there isn’t a large body of research evidence to support them. D-cycloserine is an antibiotic that at high doses acts on the same NDMA receptors that ketamine works on. Minocycline is another antibiotic that has shows some benefit, as it calms inflammatory microglia in the brain. I wouldn’t be all that keen to use an antibiotic for a prolonged period, particularly when there’s not much evidence to back it up. Infliximab, which is used for autoimmune diseases, has shown some antidepressant effect in depressed people with elevated levels of inflammation. As a biological agent, it is quite expensive. Botox has also been shown to be helpful, and I feel like I’ve had some positive results from it.
Scopolamine, which is used for nausea, appears to have an antidepressant effect via its action on muscarinic receptors in the brain. Studies have primarily involved 3 doses via IV infusion, with a rapid but not sustained effect. This is something I’ve considered trying in the form of an intramuscular injection, as the oral version of scopolamine that’s available in Canada can’t cross the blood-brain barrier to enter the brain.
Blocking kappa-type opioid receptors has been associated with an antidepressant effect. This is different from the µ-type opioid receptors which are associated with effects like analgesia and respiratory depression. Buprenorphine, which is found in Suboxone, is a kappa antagonist but also has effects on µ receptors, and research is being done to develop drugs that are selective for kappa receptors with no activity at µ receptors.
There are a number of over-the-counter supplements which have shown some effectiveness in depression. These include L-methylfolate, which may be most useful in those with elevated inflammation or impaired methylation cycles, S-adenosyl methionine (SAMe), omega-3 fatty acids, creatine, and n-acetyl cysteine, which decreases oxidative stress. I take L-methylfolate along with vitamin B12 by injection every 2 weeks, and have noticed that if I go longer than 2 weeks my thinking and my energy start to slow down. I also take omega-3’s, although I’m nor sure if it’s actually helping me or not.
Other options involve the application of energy to the brain. Probably the best known is electroconvulsive therapy (ECT). ECT has been helpful for me in the past, but it’s difficult to manage on an outpatient basis, both because of the effects on memory and because you’re required to essentially have a babysitter on ECT days. Another option is transcranial magnetic stimulation (TMS), which stimulates the brain through the creation of a magnetic field.. It has demonstrated good results in research studies, and because there’s no anaesthesia involved that decreases the pain-in-the-butt factor compared to ECT. It brings about its own pain-in-the-butt factor, though, as it’s more frequent, and at least where I live it’s not covered by insurance. Deep brain stimulation (DBS) is another option that I have very limited familiarity with. This involves the surgical implantation of a neurostimulator device that sends electrical impulses to target areas in the brain. DBS is also used for other conditions including Parkinson’s disease. The potential complications sound a bit frightening, but a quick google search shows it’s the most common operation performed for Parkinson’s Disease at the major local hospital in my area.
How is your treatment working for you? If it’s not working, what other options have you considered?
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I love Canada, but sometimes we’re a little behind. Drugs are slower to get approved by Health Canada compared to the US, and we have fewer clinical trials going on here. I would be really interested in trying out ketamine, but it doesn’t have Health Canada approval for use in depression, there are no clinical trials in my neck of the woods accepting new patients, and going to a private clinic in the US would be extremely expensive. So for now, all I can do is dream of ketamine. But in the meantime, what is ketamine and how does it work?
Ketamine has been in use for some time as an anaesthetic drug, and it has been abused as the club drug Special K. In the last several years multiple research trials have shown that it has a rapid onset antidepressant effect (within about 24 hours). It increases rates of remission in major disorder, but the effect is not as pronounced for bipolar depression. It appears to have a protective effect against suicide, and unlike many antidepressants it doesn’t appear to trigger mania.
It has a different mechanism of action than other antidepressant medications. It acts on NMDA and AMPA receptors, affecting the balance between the calming neurotransmitter GABA and the excitatory/stress neurotransmitter glutamate. It also boosts production of BDNF (brain-derived neurotropic factor), which in turn promotes the formation of new synaptic connections in the brain. It has been suggested that people with depression may have abnormalities related to their NMDA receptors and experience what’s referred to “excitotoxicity” from glutamate overactivity.
Ketamine is typically given at a dose of 0.4-0.5 mg per kg of body weight, which is a lower dose than would be used for anaesthesia, with 1-2 doses per week. The effect from each dose typically lasts 3-7 days, but can last up to 15 days. It can be given as an intravenous infusion, or the esketamine version of the drug is available as a nasal spray.
Apparently side effects are generally mild and wear off within 2 hours. While harmful effects to the bladder can occur at high doses, this hasn’t been demonstrated at the doses used for depression treatment. It can have dissociative effects while the drug is being infused and in that 2 hours window after the dose, which could potentially limit the tolerability for some people. It can trigger spikes in heart rate and blood pressure, as well as headaches, dizziness, blurred vision, drowsiness, abnormal sensations, and perceptual disturbances. Patients remain in the clinic for a period of time following the dose so that they can be monitored.
What are your thoughts? Have you had any experience with ketamine?
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The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial studied 2876 people with major depressive disorder to evaluate their response to depression treatment in a real-world setting. Unlike the randomized controlled trials that are often used to evaluate a drug’s efficacy, there were few exclusion criteria, the patient and their physician knew which drug they were taking, and patient choice was incorporated. Four sequential levels of treatment were established, and if a patient failed to achieve remission after 12-14 weeks, they would be moved to the next level. The target was full remission, unlike many other studies which measure response (i.e. a ≥50% reduction in symptom rating scale scores). Remission rates can be substantially lower than response rates, but are useful because there are better long-term outcomes for people who do achieve full remission.
Level 1 treatment consisted of citalopram, and 28% of patients achieved remission based on the Hamilton Rating Scale for Depression (HAM-D). Certain factors were identified, such as other comorbid mental illnesses, that were associated with lower or higher remission rates.
In level 2, patients were offered cognitive psychotherapy, a switch to another antidepressant (randomly selected), or the addition of another medication to augment the treatment. Among level 2 patients who switched to another medication, remission rates were 21.3% for bupropion, 17.6% for sertraline, 24.8% for venlafaxine. Rates were similar among those patients who switched to cognitive psychotherapy. Among the patients who received augmentation treatment, the remission rates were approximately 30% for both bupropion and buspirone. Augmentation with medication produced more rapid remission than augmentation with cognitive psychotherapy.
In level 3, patients who switched medication were randomly assigned to mirtazapine or nortriptyline, and patients who received an medication for augmentation were randomly assigned to lithium or the T3 form of thyroid hormone (liothyronine). Remission rates were 12.3% for mirtazapine, 19.8% for nortriptyline, 15.9% for lithium, and 24.7% for thyroid hormone.
In level 4, patients were randomly assigned to switch to either tranylcypromine (an MAOI antidepressant) or venlafaxine plus mirtazapine. Remission rates were 6.9% for tranylcypromine and 13.7% for venlafaxine plus mirtazapine.
Altogether, 67% of patients were able to achieve remission. The study found that people may still remit by 12 weeks even if there’s only a modest symptom reduction at 6 weeks. However, the more treatment steps that are required, the lower the chance of a patient achieving remission and the higher the chance of intolerable side effects and relapse.
Personally I found the take-home message from this study rather discouraging. During my last hospitalization I argued that my suicide attempt was supported by the STAR*D’s not so subtle hint that I was shit outta luck. I think it’s crucial that we find new kinds of treatment that will help that 33% of people who are treatment-resistant and just aren’t achieving remission with many currently available antidepressant medications. This study doesn’t consider all potential treatments; for example, atypical antipsychotics, ketamine, and ECT aren’ included, and psychotherapy plays a limited part. Still, we deserve better. A lot better.
For more info on the research terminology I’ve used in this post, see my post on research literacy.
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A recent paper published in the Lancet looked at how effective antidepressants are, and this has been reported on in the media. Since media outlets don’t necessarily have strong research literacy, let’s take a look at what the paper itself has to say. My earlier post on research literacy explains some of the terms I’ll be using here.
Full reference details for the paper:
A systematic review involves collecting a body of relevant literature on a topic using academic databases and search terms that are clearly specified, and then narrowing that down by applying certain criteria to find studies that are academically rigorous and fit with the research parameters being considered. Typically, different investigators go through this process independently and then come to a consensus on which studies to include in the review. The results are then evaluated to get a picture of the current state of the evidence. A meta-analysis goes a step further by pooling the data from the various studies and then performing statistical analysis.
The outcome measures were response rate and acceptability (as measured by number of discontinuations due to side effects). While ideally patients should be treated to full remission of symptoms, response rate is often used in research studies. Response rate is defined as a 50% reduction in score on a standardized depression rating scale such as the Hamilton Depression Rating Scale (HAM-D). For this meta-analysis they chose to evaluate outcomes at the 8-week point, and for the included studies that didn’t take ratings at 8 weeks this was imputed using statistical methods.
And what does all of this mean? It’s important to keep in mind that a systematic review/meta-analysis such as this is only aiming to tell us very specific things. The authors are deliberately comparing apples to apples so they can pool large groups of numbers and draw conclusions from that. There’s a lot of real-world information that it doesn’t give us, but it’s worth keeping in mind that it makes no claims that it is. The authors do not suggest that their findings can be extrapolated to answer any of the questions I’ve mentioned that the paper doesn’t give us information about. What it does tell us is that antidepressants belong in our arsenal of available treatment strategies. Anything more specific than that always needs to be a collaborative decision between the individual and their treatment team.
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I have always been a big fan of the documentary program The Passionate Eye on CBC, Canada’s public broadcaster. Until now. On January 6, 2018, they aired “A Prescription for Murder?”, which was originally shown on the BBC; links are at the bottom of this page. The program focused on James Holmes, the young man who shot and killed 12 people and injured 70 in a movie theatre in the United States in 2012. The central argument is that the SSRI (selective serotonin reuptake inhibitor) class of antidepressants can, in rare cases, cause people to become psychotic, violent, and homicidal.
According to the documentary, Holmes first started seeing a psychiatrist at his university’s student wellness centre 17 weeks before he committed the murders. He reported social anxiety and intrusive thoughts of killing people; these thoughts were not new, but it was the first that he had disclosed them. After the killings, he told a psychiatrist that he had experienced thoughts of killing people since his teens as a sort of social avoidance strategy. The psychiatrist at the wellness centre started him on the SSRI sertraline, at a dose of 50mg per day. Not long after, he described a theory he referred to as “human capital” that involved intentions to kill people. The dose was increased over the next 4 weeks to 150mg per day, as his intrusive thoughts were increasing. A little under 3 months after starting sertraline, he had made the decision to drop out of school, and declined his psychiatrist’s offer to continue treatment and start him on an antipsychotic. It is not clear when he stopped taking the sertraline, but his last prescription would have run out 3 weeks before the shootings. The journalist argues that because of the timing it is likely that Holmes’ homicidal behaviour was triggered by the sertraline. Various psychiatrists are interviewed for the film, with several expressing the belief that the sertraline had triggered psychosis, which led to the killings. One went so far as to suggest that if Holmes hadn’t been put on sertraline the murders might not have happened.
The documentary bothered me on multiple levels. If someone wants to make a film arguing that SSRIs can trigger psychosis and people should be aware of that, okay, so be it. But the choice of title is clearly intended to be sensational, as is the tagline “Is it possible that a pill prescribed by your doctor can turn you into a killer?”. On the Canadian broadcast that I viewed, on multiple occasions a banner ran across the top of the screen warning that people should not stop taking their medication without first seeking medical advice. It seemed utterly absurd to be including this message for a film arguing that SSRIs turn people into mass murderers. If one pays enough attention, the more nuanced argument being made is that SSRIs can cause psychosis and this can precipitate homicidal behaviour; however, what’s missing is the key piece of information that the probability of a psychotic person committing homicide is extremely low. That is a very different can of worms than simply connecting SSRIs and homicide.
Another flaw in the argument that is never acknowledged is that temporal correlation, i.e. things being related in terms of timing, does not necessarily imply causation. I’ll talk more about this in an upcoming post about research literacy, but it is flawed logic to think that because Mr. Holmes took sertraline shortly before he committed a mass shooting, the only or best explanation is that the sertraline caused it. The documentary does not even touch on alternate explanations, the most obvious (at least to me) being that he was started on the medication because he was getting sick, it didn’t work, he got sicker, and he became psychotic, which triggered him to act on thoughts he admitted he’d been having for years.
I worry that some poor person with mental illness is going to watch this and think oh, I don’t want to be on a medication that’s going to make me a killer. And maybe that person will stop the SSRI they are already taking, or avoid going to see a doctor to seek help for distressing psychiatric symptoms. Maybe that will mean they get sicker. And maybe, just maybe, that could have disastrous consequences like suicide. I have no hesitation whatsoever in saying that the risk of suicide from a depressed person not taking an antidepressant is higher than the risk of someone taking an SSRI and committing mass murder. There is no indication that the filmmaker has given any thought to these sorts of outcomes that could snowball in response to the messaging that antidepressants can turn people into murderers.
There also seems to be no consideration given as to how this documentary might affect public attitudes toward mental illness in general and psychiatric medication in particular. There is already more than enough stigma around this, and I for one do not want some random idiot thinking that I might fly into a homicidal rage because of my antidepressants. Someone who hasn’t lived with mental illness might think this concern is overblown, but the stigma around taking psychiatric medication is very real, as is the potential of this stigma to cause harm. By choosing to air this documentary, the BBC and CBC have chosen to move backwards in terms of stigma, exactly the opposite of where those of us blogging about mental health are trying to go.
I’m sickened by how irresponsible the BBC and CBC are for broadcasting this documentary. The same issue could potentially have been explored in a way that utilized much safer messaging. Being cynical, I’m guessing that this particular approach was chosen in order to generate buzz and viwership. I can only hope that it won’t do as much damage as I think it has the potential to.
Despite what the title might suggest, this post isn’t about me being self-critical. I have been struggling for months with cognitive symptoms of depression, and on a daily basis I notice that it impairs my functioning. But it’s not something I’ve ever had much of an objective sense of.
Until yesterday. As a nurse working in psychiatry, I need to keep up my knowledge base, and my preferred way to do that is by watching webinars. I decided I would get going right away for 2018, and watched a presentation on depression and cognition by Dr. Roger McIntyre, a professor of psychiatry at the University of Toronto who does some really interesting research. So much of what he said resonated that I felt like he was talking about me. He mentioned one study that found that people in their mid-thirties experiencing performed about the same on cognitive testing tasks as people with a blood alcohol content of 0.08 (legally impaired to drive). Hmm, sounds about right.
Dr. McIntyre and his colleagues recently developed a tool called THINC-it to objectively evaluate cognitive performance in people with depression. There are 5 elements: a short patient self-report, and then 4 different computer-based cognitive tasks. As soon as I finished the webinar, I downloaded the THINC-it tool and gave it a go.
My results are in the picture above. The ball on the left is my self-report of cognitive symptoms, and the next four balls represent the four different tests. Green is good, and red is bad. I performed abysmally.
It’s interesting to see an objective reflection of what I have been feeling for some time now. It’s hard to be confident in my perspective of my own impairment when I’m stuck in the middle of it. I do recognize, though, that I’m much lower functioning than I used to be, and the difficulties I have with basic tasks don’t match up with my high IQ and graduate degree.
One thing that Dr McIntyre mentioned that I’d heard before in other webinars is that vortioxetine is the only antidepressants that’s been show to improve cognitive functioning across multiple domains independent of its effect on mood. I was actually saying to my doctor just the other day that maybe I should consider vortioxetine, but I’m not keen on rocking the boat by switching up my antidepressants.
Having the confirmation of this test, though, makes me think a little more strongly about making a change. Depression is bad for the brain; there are cumulative neurodegenerative effects, and outcomes are worse for people who don’t achieve full remission between episodes. For me right now the most prominent symptoms I’m having are cognitive, and while my current meds help somewhat, it just doesn’t look like they’re going to fully treat these symptoms.
So maybe it is time to try vortioxetine. Yet the idea of a major med change terrifies me, because it was so hard to hit on this particular combo when I was really sick 5 years ago. This is perhaps the only time I have regretted that I’m seeing a family doctor rather than a psychiatrist. I’m really happy with my doctor, and for the most part I’ve liked that I tell him what I’m considering and he gives me feedback on what he thinks is the best choice. When it’s something as big as this, though, a part of me wishes for someone who’s up on the latest knowledge in the field to take the lead. Then again, I don’t trust very easily, and I trust my current doctor.
I’m not sure what I’ll decide, but I think I should make sure that I’m not just accepting the status quo by default.
The title is a kind of weak ripoff from the Seinfeld-ian Pimple Popper MD, but still, it’s fairly apt. I have major depressive disorder, and I take a boatload of pills. Because my memory isn’t that great and I don’t want to forget to take them, I have them all laid out on a shelf in my bookcase. If anyone comes into my living room chances are they’ll notice the mini pharmacy I’ve got going on, but I am so beyond caring about what people think about that.
In this post I’m going to break down the various things I’m putting into my body to try and stay afloat with my depression. Medications will never be all of the picture, but for me they are an important part of my treatment plan.
Mirtazapine 30mg and venlafaxine 300mg: These are my two antidepressants. I have always responded better to antidepressants with more activity related to norepinephrine than serotonin, so these two fit the bill. The combo is sometimes referred to as “California rocket fuel” because of its potency. Mirtazapine is actually most sedating at lower doses, so I’ve settled on the middle of the road 30mg dose because I didn’t sleep as well on higher doses.
Lithium 1200mg: I don’t have bipolar disorder, but lithium has actually been recognized for a long time as an effective augmentation strategy in major depressive disorder. If I start feeling worse one of the first things my doctor and I consider is increasing my lithium, since I tend to respond fairly quickly to dose increases. When my serum levels get higher, though, I tend to have increased problems with tremor and coordination, turning me into a complete klutz, complete with wipeouts on the sidewalk and falling down stairs.
Quetiapine 600mg: Atypical antipsychotics are also effective for treatment augmentation in depression. Of the ones I have tried, quetiapine has been most effective for me. It helps with my mood and is very reliable for getting to sleep.
Dextroamphetamine 15mg: I first tried dextroamphetamine a year and a half ago when I was really slowed down in both movement and thinking. It helped, but I wasn’t keen on taking “speed” any longer than needed, so I only took it for about a month. I restarted it earlier this year when I got really slowed down again. It helped, but when I tried to decrease the dose my mood dropped. Research has shown that it tends to be effective as an antidepressant augmentation strategy for only a couple of months or so, and then the effect tends to wear off; however, I’ve tried several times to decrease the dose and it makes me feel worse. My doctor has a good attitude about it, and has no problem with me taking it on an ongoing basis when it’s clearly working.
Propranolol 10mg prn (as needed): Lithium gives me an intention tremor, which occurs with intentional movement as opposed to a resting tremor. It’s worse if my lithium level is higher or if I’m worn out, and probably the dextroamphetamine doesn’t help either. Propranolol helps keep it in check, and I tend to use it mostly for days that I’m working, since patients generally aren’t reassured about getting an injection if the nurse drawing it up has shaky hands.
Lorazepam 0.5-1mg prn: Anxiety is generally not a prominent feature of my illness, so I’ve never needed to use lorazepam (Ativan) on a regular basis. I find for me it’s most effective to get a bit of a numbing effect when I’m going into particularly stressful situations. Since I use it so seldom, I’m able to get away with a small dose.
Min-Ovral: I have spent much of my adult life on birth control, but decided a couple of years ago to take a break. When I got depressed last year, my hormones went crazy. I was getting my period every 3 weeks and PMS was having a big impact on my mood. Now I’m back on birth control and my hormones are steady and happy. The estrogen in the Min-Ovral may also give my neurotransmitters a bit of a boost.
Omega-3 fatty acid plus vitamin D supplement: There have been research studies that have shown that omega-3’s have some beneficial effect on depression. Vitamin D may also play a role in depression, and since I live on the Wet Coast of Canada where it rains for a good chunk of the year supplementation seems like a good way to go.
Multivitamin/mineral/antioxidant supplement: Besides helping my overall health, the goal with this is to have some effect on decreasing oxidative stress, which may play a role in depression.
L-methyfolate and vitamin B12 supplementation: I get these in an intramuscular injection every 2 weeks from my naturopath. Both play a role in the methylation cycle that’s involved in neurotransmitter synthesis, and L-methylfolate in particular has been shown to be useful in depression.
So that’s me, Pill Popper RN. What’s in your medicine cabinet?
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I can be a bit (okay more than just a bit) of a geek, and one of my big interests is how medications work. Throw in the fact that I’m a mental health nurse, former pharmacist, and person who has tried piles of different psychiatric medication, and you get someone who will quite happily watch hours of continuing education webinars on the topic.
It can be really useful to understand how medications work, because it can make both the therapeutic effects and side effects make more sense. This is the first of a series of psych meds 101 posts I’m going to write that will break down different classes of medications. I’ll also address antipsychotics, mood stabilizers, anti-anxiety meds, and sleep meds.
Most antidepressants affect the three major neurotransmitters implicated in depression: serotonin, norepinephrine, and dopamine. Nerve cells (neurons) communicate with other neurons via connections known as synapses. The neuron sending the signal is referred to as presynaptic, and the neuron receiving the signal is referred to as postsynaptic. The presynaptic neuron releases neurotransmitter molecules in the synaptic cleft (the space between the two neurons), and the neurotransmitters act at specific receptors on the postsynaptic neuron.
Why does that matter? Many antidepressants are reuptake inhibitors, meaning they block recycling pumps on the presynaptic side that would normally take up and recycle some of the neurotransmitter that had been released. This means there is more neurotransmitter floating around the synaptic cleft, available to act at receptors on the postsynaptic neuron. Over time, this actually changes the number of receptors that the postsynaptic neuron produces, which may explain the delayed onset of action for antidepressants.
Other antidepressants may block certain types of receptors on either pre- or post-synaptic neurons, and this may influence the release of one or more types of neurotransmitters.
A lot of medications are messy, in the sense that they don’t only do want them to. Some antidepressants affect histamine receptors, and this can cause side effects such as sedation and weight gain. Activity at muscarinic receptors can cause sedation, dry mouth, and constipation.
There are multiple different kinds of serotonin and norepinephrine receptors, and they impact various processes in the body. When serotonin gets busy at certain types of receptors it can do things that we don’t want it to, causing things like insomnia, weight gain, or sexual dysfunction. Norepinephrine can act at certain receptors to affect things like blood pressure, causing lightheadedness.
These inhibit the activity of the presynaptic serotonin recycling pumps. Escitalopram is the most “clean” in that it does what it’s supposed to and not much else. Other medications in this class include citalopram, sertraline, fluoxetine, and paroxetine.
These inhibit the presynaptic recycling pumps for both serotonin and norepinephrine. Some people are not as responsive to meds that act on serotonin alone, and respond better when there is action on norepinephrine. Drugs in this class include venlafaxine, desvenlafaxine, and duloxetine.
Bupropion inhibits the presynaptic recycling pumps for norepinephrine and dopamine. Because of the different mechanism of action, it can be used in combination with SSRI for a triple-whammy sort of effect.
These inhibit the recycling pumps for serotonin and norepinephrine. However, they are quite “messy” and affect a number of different receptors, meaning they tend to cause more side effects. They are dangerous in overdose because they can potentially disrupt the heart rhythm. Several years ago a psychiatrist wanted to put me on nortriptyline, and while I reluctantly agreed, I soon stopped it because I didn’t think it was a safe medication to have at home given that I do get suicidal thoughts in the context of depression. Other examples of TCAs include amitriptyline and imipramine. This class of medications is also used to manage nerve pain.
These inhibit the monoamine oxidase (MAO) enzyme, which acts inside neuronal cells and is involved in breaking down serotonin, norepinephrine, and dopamine. They are an older class of medications and despite being very effective antidepressants they are seldom used because of the need to restrict dietary intake of tyramine. Tyramine is normally broken down in the gut by MAO, but if MAO is blocked by medication, tyramine is absorbed into the bloodstream and sends blood pressure through the roof. This condition is referred to as hypertensive crisis. Tyramine is found in a number of different foods, including aged cheeses and fermented foods.
Tranylcypromine is the most commonly used MAOI. Moclobemide is a variation of an MAOI called a RIMA (reversible inhibitor of monoamine oxidase) that acts reversibly on the MAO enzyme, so that tyramine is still able to get broken down safely by MAO in the gut.
There are a variety of other medications such as mirtazapine and vortioxetine that work in novel ways, which I won’t get into here. The combination of mirtazapine and venlafaxine is sometimes referred to as “California rocket fuel”; this is part of my current treatment plan, and while I’m not getting a rocket fuel effect it has helped. There are also other medications that can be used to augment antidepressant therapy, including lithium, atypical antipsychotic medications, and liothyronine (a form of thyroid hormone).
There are also new outside of the box treatments being studied such as ketamine, which affects the action of the neurotransmitter glutamate. I am really excited about this, and will write more about it in future posts.
If you’ve made it this far, good for you! I hope you’ve found some of this useful, and maybe it’s even given you some added insight into medications you have taken or are taking. In the upcoming post Psych Meds 101: Mood Stabilizers, I’ll talk about the treatment of bipolar depression, and why antidepressants have a limited role to play.
I guess I should start by explaining what Uzbek is. It’s the language of Uzbekistan, a former Soviet republic in central Asia that was part of the Silk Road that once wound through Asia. It’s an area of the world where there are still people living the traditional nomadic lifestyle involving yurts, riding horseback, and drinking fermented mares’ milk (a delicacy I just couldn’t bring myself to try).
So how does this relate to antidepressants? That’s where I have a story to tell. In 2015, I spent 5 weeks backpacking in Uzbekistan, Kazakhstan, and Kyrgyzstan. During that time, I was hauling around a veritable pharmacy: a sufficient supply of my 5 different psych meds, plus my standard round-up of just-in-case backpacking meds to cover motion sickness, travel’s diarrhea, and other such fun adventures.
I landed in Tashkent, the capital city of Uzbekistan, around 10pm. I was exhausted from the long flight, and just wanted to fall into bed somewhere. I thought it seemed a bit odd that the customs declaration form asked for a list of any medications I was carrying, but I dutifully listed them all. The rather ghetto-seeming airport wasn’t inspiring much confidence, but I hoped that as is often the case my Canadian passport would get me waved right through.
When my turn in line came, I handed my declaration form to the customs officer. He stared confusedly at my mammoth list of medications. Then he wanted to see them, although I’m not sure why, as that didn’t seem to make things any easier. He appeared to have no idea what to do, so he consulted some of his colleagues. I told them that they were for depression, but they didn’t seem to have any idea what I was talking about. There was much talking, looking confused, and phone calls until finally they waved me along.
I thought that would be the end of it; if only I could be so lucky. I hadn’t booked a hostel room because it hadn’t struck me as necessary; I was an experienced traveller and had never had problems before. Tashkent is no great tourist mecca, so that might have worked out okay, except there was some sort of international sporting competition going on in town and everything was booked up solid.
By midnight, I had given up on Tashkent and instead turned up at the Uzbekistan-Kazakhstan border, thinking I might have better luck across the border. Except that meant another customs declaration form, and much more confusion over my bag of meds. The customs officers tried to be nice, but spoke very minimal English. They wanted to know what the meds were for, and I didn’t think antidepressant would be in their lexicon, so I kept pointing at my head. Maybe that made them more confused, or maybe it made me look more like a psych patient – who knows. When they saw I’d just arrived in Uzbekistan that night, they decided they needed to call customs staff at the airport. Talk about the blind leading the blinder. Eventually I think they just took pity on me and let me go.
Travelling with psychiatric medications in non-Western countries can be a bit dicey, even aside from the issue of border crossings. Replacement meds can be hard to come by if meds get stolen, and that’s something I always try to remain cognizant of. That saved my butt on one occasion in India when I was sleeping in an upper bunk on an overnight train. My backpack was shoved underneath the lower bunk, and during the night someone stole everything in the backpack other than clothing. If my bag of meds hadn’t been tucked in beside me on the bunk, they would’ve been gone.
I haven’t really been well enough to travel in the last couple of years, but hopefully I’ll get back into it even with the depression. I still may be able to pull off my 40 by 40 goal: 40 countries visited by age 40. And next time I go somewhere off the English-language track, I might look up the local word for antidepressant ahead of time… just in case.
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What do mental illness and sex have to do with each other? Quite a bit, actually, both in terms of the illness itself and the medications to treat it.
Let’s start with meds. Antidepressants that affect serotonin (such as the SSRI class) can do a real number on sex drive/function. This tends to be mediated by a particular type of serotonin receptor known as 5HT2a, which means that some antidepressants that affect serotonin are less likely to cause this problem, such as mirtazapine and vilazodone. Another option is something like bupropion, which doesn’t act on serotonin receptors. I talk more about antidepressants in my psych meds 101 post.
Antipsychotics can also be problematic (more on this in psych meds 101). Antipsychotics work by blocking dopamine receptors, but if there is too much dopamine blockade along a certain pathway in the brain (the tuberoinfundibular pathway to get really geeky with it), you disrupt levels of the hormone prolactin, and boom, you get sexual dysfunction. Different antipsychotics vary in their potential to affect prolactin, so having sexual side effects with one doesn’t mean you will necessarily have the same effect with another medication.
Some mood stabilizers such as valproic acid are quite teratogenic, meaning they’re likely to cause fetal malformations. This means reliable birth control is something that has to be considered along with everything else that goes with a mood disorder. This is easier said than done for a woman in the midst of a manic episode.
Then there is the illness itself. As a nurse, I’ve spoken to clients who are deeply ashamed of reckless sexual behaviour they’ve engaged in while manic or psychotic, things that under normal circumstances they would never even consider doing. At the other end of the spectrum, depression can shut down sex drive and sexual function. These are issues that it’s not easy or comfortable to talk about, so they tend to hide in the shadows, but they can have a huge effect both on an individual level and on a relationship. I don’t have any great insights or answers to share with you, but I do think it’s important to talk about it. It’s also worth considering sex as a potential barometer of your mental health. I remember at one point when my depression was starting to improve I met a man who actually made me feel turned on, and I thought wow, this is the most normal thing that I’ve felt in a very long time.
I’ll close with a quick word on autoerotic activity, to borrow a term from Seinfeld. Orgasm releases happy hormones like oxytocin and dopamine, so it seems to me a little bit of self-love once in a while can’t hurt. And really, we all deserve some self-love, whether it’s in an erotic sense or not.
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