This gets a little technical, but it’s also really important in understanding how most antidepressants (and atypical anti-psychotics) work, so put on your best thinking hat and read on.  Each antidepressant is made up of molecules that bind themselves to various receptors and systems in our brain, and affect those systems in some way.  Most antidepressants we use tend to work because of the ways in which they affect specific systems and neurotransmitters in our brain, most notably serotonin, norepinephrine and dopamine.  However, and this is the important bit, these are not the only neurotransmitters and receptors in our brain that are affected.  Each antidepressant has what are called ‘affinities’, which are basically preferences of where it will go in the brain once it gets into your bloodstream.

Imagine a parking garage made up of multiple floors.  Each floor represents one of the systems or receptors in your brain, and has a limited number of parks.  A molecule of an antidepressant works kind of like a car that comes to the parking garage looking for a park.  In this case, let’s imagine that the car is Amitriptyline, a particular antidepressant.  Amitriptyline’s first preference is to bind to the H₁ receptors in your brain, so in our parking-garage analogy this would be the first floor of the garage.  The first molecule comes along, finds a park in the first floor and all is well.  The next molecule does the same, and so on.  Eventually though, this floor of the garage fills up and the next molecule that comes along can’t find a park – what happens then?  Well, then it looks for the next most preferred place to park, in this case probably the serotonin transporter protein.  The next few molecules do the same until this floor is filled up, and then subsequent molecules have to find a park somewhere else.  This continues on until all possible ‘parks’ in the parking garage are full.

The reason this is important to understand is that these different receptors in the brain/levels in our parking garage do very different things.  In the case of the H₁ receptor in the brain, the effect of Amitriptyline on this receptor is to make you sleepy.  The effect of Amitriptyline on the serotonin transporter protein is to make you feel better (hopefully).  So what this means is, if you take a really low dose of Amitriptyline, all of it will just fill up the parks at the bottom of the parking garage (the H1 receptor) and all you’ll get is that you feel sleepy.  It’s not that you don’t get much antidepressant effect, it’s that you get absolutely no antidepressant effect because all the molecules of the drug are going first of all to a receptor in the brain that influences sedation.  If you then increase the dose, you’ll start to get an antidepressant effect.  If you continue to increase the dose past a certain point, you won’t get any more antidepressant effect because that level of the parking garage is now full, and subsequent molecules will bind to receptors that create different side effects (or do nothing).  This is why getting dosing right with antidepressants is so important, because increasing or decreasing the dosage can be less about increasing/decreasing the effect of the drug and more about introducing completely different effects.  It also means that you won’t get more of an existing effect beyond a certain point – which means just because you’re experiencing a side effect from a particular drug does not mean you will experience more of that side effect if you increase the dosage.

So what do all these drugs do then?  Well, starting with the most common:

SSRIs

Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants are the most commonly prescribed antidepressants in New Zealand (including Fluoxetine, Citalopram, Escitalopram, Paroxetine and Sertraline).  These work by affecting the serotonin receptors and transport systems in the brain in ways that are far too complicated for me to get my head around, and which are still not fully understood even to psychiatrists working specifically in this area.  We know that serotonin is somehow involved in some forms of depression, but exactly how is unknown – it’s not as simple as ‘not having enough’ when it comes to levels of specific neurotransmitters in the brain.

These are generally tried first before any other antidepressants due to their generally lower risk of side-effects.  However, there are some very common side effects experienced with these drugs including (with reported rate of likelihood):

56% decreased sexual functioning (reduced libido, anorgasmia, delayed ejaculation)
53% drowsiness
49% weight gain
19% dry mouth
16% insomnia
14% fatigue
14% nausea
13% light-headedness
12% tremor

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719451/)

These numbers are averaged across multiple SSRIs, so may vary from one drug to the next.  The ‘selective’ part of SSRI refers to the fact that these drugs are more selective about binding to the receptors in the brain associated with their antidepressant effect.  If we go back to the parking garage analogy, they look for the parking spaces that have to do with serotonin (which affects mood) more than the spaces to do with other effects.  The fact that some of these side effects still occur for a majority of people relates to the fact that they’re not perfectly selective, so some binding to other receptors in the brain still occurs.  However, the idea is that they’re more selective than older antidepressants like tricyclics.

One other common feature of SSRIs that is worth being aware of, particularly if you’re taking them for the first time, is that they usually take up to six weeks to take full effect.  During this time it is not uncommon to experience increased anxiety, including racing thoughts, increased heart-rate, jitteriness or trouble sleeping.  These symptoms often subside after the initial period, but can lead to people stopping taking the medication before it has a chance to create a positive effect.

SNRIs

Another reasonably common class of antidepressants are Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs).  These work on the serotonin transporter proteins (the same as SSRIs) but also affect the norepinephrine transporter protein which is also indicated in affecting our mood.  In New Zealand, the most common SNRIs I’m aware of being prescribed are venlafaxine and duloxetine.  SNRIs tend to create very similar side-effects to SSRIs due to very similar mechanisms of action.

Tricyclic Antidepressants

Tricyclic Antidepressants (TCAs) are older antidepressants and were some of the first to be used to treat major depressive disorder.  These medications include things like nortriptyline, amitriptyline and imipramine.  TCAs have usually been shown to be just as effective as more modern SSRIs and SNRIs, but are typically used less often due to increased side effects.  This increase is due to the fact that tricyclic antidepressants bind preferentially to a lot more receptors and systems in the brain than SSRIs do – that is, they’ll fill up the parks to do with sleepiness/sedation before you get an antidepressant effect, which is why they are sometimes used as sleep aids in low doses.

Some studies have shown TCAs to be more effective than SSRIs in the treatment of melancholic depression  (a particularly serious and debilitating form of depressive disorder), and some people find that they do not particularly notice or are not affected by the sedative effect of TCAs.  For this reason, they are still quite commonly used.  If you suffer from severe depression and have tried a range of SSRIs without any effect, then it can definitely be worth trying a tricyclic antidepressant as it may be that you are more responsive to these than to SSRIs.

MAOIs

The last type of antidepressant I’ll talk about and probably the least prescribed in New Zealand are Monoamine Oxidase Inhibitors (MAOIs).  The most common MAOI I’m aware of being used in NZ is moclobomide, but there may be others.  In a different way, MAOIs also have an affect on serotonin, dopamine and norepinephrine in the brain – all antidepressants tend to work on these systems, but in different ways and with different degrees of preference.  MAOIs tend to be used infrequently in the treatment of depression due to the fact that they have potentially lethal interactions with certain foods and other medications, although recent research has called this into question and shown that at least some of these interactions have been over-stated and are less dangerous then previously thought.

MAOIs have been shown to be effective in the treatment of depression, and are sometimes prescribed for this reason when SSRIs and TCAs have been tried without effect.  Due to a somewhat different mechanism of action, they can be effective when other medications have not been.  As long as people taking them are mindful of the dietary restrictions and other potential interactions, MAOIs can be a useful treatment option and for some people produce fewer side effects than other medications.

Conclusion

Hopefully this gives you a bit of an idea about what to expect and the options available in terms of antidepressants in New Zealand.  There are a few other medications available including atypical antidepressants like Buproprion which I haven’t mentioned as these are generally not used unless other treatments have been ineffective, but I’ve covered the major types that are used in treatment.  As I stated in my first article about psychotropic medication, these medications can be both enormously helpful for some people, and worthless or problematic for others.  The general principle of ‘what can help can harm’ applies here – particularly since as discussed, these medications affect other systems in the brain apart from those that are just to do with mood.  I really encourage anyone taking or thinking of taking antidepressant medication to research how it works, the side effects for that particular medication, and to record for yourself what you notice in terms of both positive and negative changes.  The more you can become aware of your own responses to medication, the more you will be able to help your prescriber make choices about what best to prescribe if the first things you try are not effective.

Then there are the reports about psychotropic medications in the media, such as recent studies that suggested that common anti-depressants are little more effective than placebo.  Finally, there’s still a lot of stigma for some people around taking psychotropic medications, and various messages that some health professionals push which are intended to combat this stigma but which sometimes are inaccurate and lead to mistaken understandings about medication.  I want to address all of these points, but it will likely take more than one post to do so.  I want to start by talking about some of the general principles around psychotropic medication, and dispel some of the misinformation that is floating around as well.

1. We do not know if psychotropic medications correct a ‘chemical imbalance’ in the brain, but they probably don’t.

The truth is that we do not fully understand how pretty much any of our psychotropic medications work. Although our understanding of the brain has improved dramatically with modern neuroscience tools and technology, we are still a long way off from being able to accurately explain the link between our brains and what we think and feel, let alone explain how specific drugs affect this. We do know that certain parts of the brain are typically associated with particular types of feelings, but given the 100 billion neurons in our brain this is kind of like saying that the Waikato is largely associated with agriculture. True, but it doesn’t really tell us much about specifically what’s going on.

Our understanding is not incomplete – we know that particular neurotransmitters are affected by particular drugs, and that this is probably related to the effect that these drugs have, but we don’t know exactly how this happens – which is part of the reason why psychiatrists cannot predict which antidepressant will work best for any given person, and it can end up being a process of trial-and-error.

We know now from research into neuroplasticity (the brain’s ability to create new neural structures based on our experiences) that many mental health issues likely arise from this process.  Our brain essentially tries to adapt to difficult or challenging circumstances, often in ways that are helpful in the short term but create problems in the longer term. So while it is true that our brains do become functionally different when we are suffering from mental health issues or psychological distress, this is a very different process from the kind of chemical imbalance that might arise from, for example, having an iron or iodine deficiency that can be corrected by introducing more of these substances into your diet.

2. Even though we don’t understand why psychotropic medications work, they still do work.

Despite some studies showing that, for example, antidepressants on average are not much more effective than placebo, these medications do work and work very well for some people.  Often research done around psychological conditions can be quite misleading, since research is done across a large number of people and yet from an individual perspective the question is not ‘does this work for the majority of people’, but ‘does it work for me?’  One of the bigger studies into the efficacy of antidepressants found that on average, they had an effect size of 0.31 over placebo.  If we just look at this value alone, then it can seem fairly insignificant.  However, digging into the research a bit further we see that this effect size varied from medication to medication, with some of the more commonly used antidepressants having effect sizes closer to 0.5, which is usually deemed to be ‘clinically significant’.

More importantly though, looking at the raw data from studies like this we usually see that this average effect size comes about from the fact that some people had a strongly positive response to the drug, while others had no response, or a negative response.  That is, it wasn’t that it was mostly ineffective for everyone – it’s that it was very effective for some, and not so much (or detrimental) for others.  A more meaningful number used in medicine is ‘Number Needed to Treat’ (NNT).  This number basically says ‘you need to give this many people the drug in order for one of them to get a meaningful benefit from it’.  In the case of fluoxetine (Prozac), the NNT seems to be between about 3 and 6, depending on the population and particular study.  That is, if you give fluoxetine to 6 depressed people, one of them will probably improve significantly.  If you’re that 1 person, this is amazing.  Otherwise it kinda sucks.

But, and this is important, this is true for all psychotropic medications.  Which means that if you’re one of the five for whom fluoxetine did nothing, maybe you’re the one in 7-9 for whom escitalopram is effective (I know, I’m talking about SSRIs a lot – because they’re one of the most commonly prescribed drugs for mood disorders in New Zealand).

So while any given drug can reliably be said not to work for most people, all of the most common drugs will work for some people.  This is why it’s so important to find a GP or psychiatrist – if you’re going to take psychotropic medication – who can work with you to try different medications, pay attention to your response, and find alternatives when first attempts are ineffective.

3. Psychotropic medications do have side effects – and we need to weigh them up.

Because psychotropic medications can be effective, they can also do harm.  This is important to understand – anything that can make a positive difference also has the potential to cause harm – the same is true of psychotherapy.  I’ll talk more about the most frequent side effects of common medications in a later post, but it’s important to be aware that side effects are common with most psychotropic medications.  Again, as with efficacy some people will experience them and others won’t – you won’t know until you try.

What this means is that prescribing and taking psychotropic medications needs to be a carefully considered choice based on the possible risks vs possible benefits.  Ideally, doctors would have the time to talk through in depth with patients the possible side effects, and how they would feel if they were one of the people who did experience that side effect.  Patients could then decide if it would be worth it to them for the chance of a medication that helps, whether it’s with depression, anxiety or anything else.  Unfortunately in my experience this rarely happens – patients are often prescribed medication with little explanation, and although this information is readily available we don’t always know where to find it.

Ultimately, only you can know whether it is right for you to take psychotropic medications, and only you can know if they are helpful for you when you do take them.  The best advice I can give anyone taking or thinking about taking medication is to really ask whoever is prescribing as much as you can about what to expect, possible side effects, the number needed to treat for that medication, and the possible benefits so you can make the decision for yourself with as much information as possible.

 4. There is nothing wrong with taking psychotropic medications.

Although acceptance has grown for all kinds of treatment for mental health problems, there is still often a stigma around taking psychotropic medications.  Sometimes this is seen as a sign that there is something ‘seriously wrong’, or that you’re not capable of coping on your own.  People sometimes talk about medication being a ‘crutch’.  Although this is often said in a derogatory sense, in another sense it actually is not inaccurate.  A crutch for a broken leg is something that we use to help us manage something outside of our control for a period of time until our body heals itself enough for us to do away with the crutch.  It’s a temporary measure, designed to support and promote our body’s natural ability to heal, and to go alongside other rehabilitative measures like physical therapy.

Psychotropic medications can perform a similar role – to help us get our life to a point that’s more manageable, so that we can start making the changes and taking the steps that we need in order to return ourselves to health.  Sometimes medication can help us get to the point where we can get the most out of therapy, where we’re really able to use it.  Or it helps us get out of the house, get exercising and start doing the things that lead to us becoming psychologically healthy once more.

If you have been considering taking a psychotropic medication and have thought or felt that it’s wrong, or that there’s something wrong with you for doing so, then these are the sort of thoughts and feelings that it can be useful to discuss with your prescriber, or with a therapist.  Again, only you can know whether taking medications is something that you want to do, but if it’s something you believe might be helpful then it can be useful to explore and talk about your thoughts and feelings about that decision.