Depression is a highly crippling and actually dangerous condition that affects over 19 million American adults (almost 10%). It’s a condition that is more widespread than coronary heart disease and which left untreated can be potentially fatal.
As such there are over 20 different medications approved by the US Food and Drug Administration intended to treat depression and these can provide relief from many of the symptoms of depression while patients attempt to deal with the causes of their feelings (other drugs can also be used in treatment of depression that are not primarily classed as antidepressants). However all of these medications have different side effects and different mechanisms of actions. Others can interact with other conditions or medications that the individual may be experiencing. This is true for instance of tricylic antidepressants such as Elavil or Sinequan which are not recommended to those with heart conditions or high blood pressure.
Which medication is the most effective will depend on the individual taking it and the particular case of depression. This can make selecting an antidepressant a difficult process for someone who doesn’t know all of the facts, but the good news is that it also means there are lots of options and lots of courses of action to try. If you have attempted to use BETA blockers and been unsuccessful for instance, then you might find that you are more responsive to serotonin re-uptake inhibitors. Here we will look at how various antidepressants work and what some of the side effects may be, and this will help you to make a more informed decision with the help of your doctor, and to understand the effect that the drugs may be having on your body.
Selective Serotonin Re-Uptake Inhibitors
Serotonin re-uptake inhibitors do what they say – they prevent serotonin receptors in the brain from using up all the serotonin in your brain. This works as serotonin is a ‘feel good’ hormone which can elevate mood and improve the communication between neurons. This results in a greater abundance of serotonin and more 5-HT in the presynaptic neuron. This is the current ‘standard’ medication and includes such medications as GABA, Paxil and Zoloft. However these do have some side effects including drowsiness and erectile dysfunction in some cases. As depression itself can also lead to sexual problems this may put some people off of their use. Other potential side effects include weight gain, decreased appetite, insomnia, anxiety, dry mouth and more. Sometimes you will see serotonin re-uptake inhibitors abbreviated to ‘SSRI’ (Selective Serotonin Re-uptake Inhibitors).
Serotonin Norepinephrine Re-Uptake Inhibitors
Serotonin norepinephrine re-uptake inhibitors, known also as SNRIs, are a slightly newer drug that works on both 5-HT and norepinephrine. This then means that they may work where SSRIs are ineffective. They carry the same side effects as SSRIs, however they are also physically addictive and can cause withdrawal symptoms after withdrawal thus necessitating dosage tapering. This is also why doctors and psychiatrists may recommend SSRIs first.
There are many other forms of inhibitors that work around serotonin, noreadrenaline and dopamine in different ways. For instance you can get norepinephrine reuptake inhibitors which act only via norepinephrine, selective serotonin re-uptake enhancers, norepinephrine-dopamine re-uptake inhibitors (dopamine being another ‘feel good hormone’ related to drive and reward) and norepinephrine-dopamine disinhibitors. Doctors can try different combinations of these drugs in order to subtly alter the brain chemistry to create more feel good hormones in greater abundance and to alter the way the brain interacts with them. The precise drug prescribed may depend somewhat on the specifics of the symptoms – for instance those with problems with drive, motivation and enjoyment may be recommended norepinephrine-dopamine combinations.
Tricylcic antidepressants are the oldest form of antidepressants and these work by blocking the reuptake of neurotransmitters such as norepinephrine and serotonin too. The difference is in that tricyclic antidepressants work by blocking the serotonin transporter and norepinephrine transporter (rather than receptors). This results in extracellular concentrations of the neurotransmitters increasing neurotransmission. However these are less commonly used as they are less selective and safe than SSRIs etc. Side effects can include increased heart rate, dry mouth, drowsiness, constipation, blurred vision, confusion, sexual dysfunction, lack of libido or appetite and dizziness among other side effects. They are lethal in overdose (usually at around ten times regular dosage) and cause fatal arrhythmia. This is due to the fact that TCAs also inhibit sodium and l-type calcium channels. However despite these increased risks, tricyclic antidepressants are often effective where other antidepressants are not and so they will still find use in cases of severe depression.
Monoamine Oxidase Inhibitors
MAOIs achieve the same end goal as SSRIs and TCAs using a slightly different mechanism of action. These work by blocking the enzyme monoamine oxidase which is responsible for breaking down certain neurotransmitters including dopamine, serotonin and norepinephrine. However there are some potentially fatal interactions between MAOIs and particular foods (those containing tyramine) and certain drugs and thus MAOIs in their traditional form are very rarely prescribed. Emsam is one monoamine oxidase inhibitor which is a transdermal patch (a skin patch) which bypasses the stomach and thereby is less likely to cause such reactions and meanwhile reversible inhibitors of monoamine oxidase A (RIMAs) work in a similar but safer and more short lived manner. MAOIs however are still considered a last resort and generally are avoided.
Beta blockers are not primarily used for depression, rather they are used for the management of cardiac arryhthmias, hypertension and other heart/circulatory system conditions. They achieve this by blocking stress hormones as they are adrenergic receptor antagonists. This then in turn means that they can be used also for anxiety disorders and if this is a pronounced aspect of depression then they may be prescribed. They are also interestingly used by athletes, speakers and others as performance enhancers due to their ability to combat performance anxiety. They may also be recommended following traumatic events. Adverse effects include nausea, diarrhoea, dyspnea, cold extremities, circulation problems, bradycardia, hypotension, heart failure, dizziness, alopecia, abnormal vision, insomnia, nightmares, sexual dysfunction, erectile dysfunction and alteration of glucose and lipid metabolism.
Benzodiazepines are psychoactive drugs with a chemical structure which is the fusion of a benzene ring and diazepene ring (hence the name). These enhance the effect of the neurotransmitter gamma-aminobutryic acid (GABA) which itself is a serotonin-re-uptake inhibitor. At the same time GABA increases the amount of melatonin in the brain (the sleep hormone) and increases the production of growth hormone. This creates a sedative effect that relaxes the muscles, causes drowsiness and sleep and anti-anxiety effect which makes them useful in the treatment of anxiety disorders and some forms of depression. They are generally safe but have some negative effects in some cases such a cognitive impairment and aggression. Long term use can lead to physical dependence and addiction and as such their use is controversial. They can be used as augmenter drugs (see below) as a way to minimize anxiety in the short term.
Lithium is the use of lithium ion (Li) chemical salts as a medication for mood stabilizing. After ingestion lithium is absorbed into the CNS (central nervous system) and will interact with a range of neurotransmitters and receptors in order to decrease norepinephrine and increase serotonin synthesis (creation). This is used as the primary medication for a particular type of depression called ‘bipolar depression’ which is characterized by extreme mood swings along the spectrum – periods of ‘mania’ followed by extreme depression. They can help to reduce the incidence of suicide among such patients and are often used as augmenter drugs (see below) alongside other medications. However there are as ever some side effects including the possibility of birth defects in new born babies taken during pregnancy, weight gain, thirst, and hypothyroidism (which itself causes weight gain, lethargy, skin and hair problems and other symptoms). In some unfortunate cases lithium may also exacerbate rather than reduce symptoms of depression.
Some people will choose to shun medication and turn instead to natural or herbal forms of antidepressants. This can include mineral and herbal supplementation, diet changes such as an increase in sodium or vitamins to help improve cognitive function and immune system performance or lifestyle changes such as increased exercise which results in the release of endorphins. Things like getting more sunlight can help by increasing the natural production of serotonin, while avoiding alcohol and other drugs can also help. Doctors will usually recommend lifestyle changes with therapy before prescribing medications due to their range of side effects.
Augmenter drugs are not necessarily antidepressants in themselves, but are designed in order to increase the efficacy of other drugs and are used in combination as part of a stack. For instance they may be used alongside benzodiazepines as a way to decrease the likelihood of dependency. Benzodiazepines may themselves also be used as augmenter drugs in order to combat anxiety and insomnia. By using them in small doses alongside other drugs this also decreases the likelihood of dependency. Antipsychotics such as risperidone may also be prescribed alongside other antidepressants as a mood stabilizer, to increase the blood concentration of other drugs or to relieve symptoms such as delusions or paranoia which can sometimes occur alongside depression. Psychostimulants meanwhile such as Adderall, Tiraline, or modafinil drugs may also be used in order to counter low motivation/excessive eating and lack of socializing characteristic of atypical depression.