Case Study on Postpartum Depression
This patient, a 35 year old mother of 3, who just gave birth 8 weeks ago began to notice depressive symptoms about a month ago. Her obstetrician notices her sadness and anxiety and prescribed a low dose of Zoloft. Five weeks later, some of her symptoms have improved, but the patient says she feels worse. She now complains of worrisome weight loss and lack of sleep. Her obstetrician referred her to the psychiatric provider for treatment of possible postpartum depression (PPD).
Neurobiological Theory
Several treatments for depressive symptoms such as those that accompany PPD exist. The discovery that a reduction monoamines—norepinephrine, serotonin, and dopamine—may be a cause of depression was made in the 1950s. Since then, pharmacologic therapy for the treatment of depression has focused on increasing the brain monamine concentration. Norepinephrine, serotonin, and dopamine are neurotransmitters and are normally found in low concentrations in gamma aminobutyric acid (GABA), a neurotransmitter that blocks impulses between nerve cells in the brain. Goldberg, Bell and Pollard (2014) writing in Perspectives of Medicinal Chemistry list evidence that a deficiency of GABA may contribute to depression including magnetic resonance spectroscopy of parts of the brain show that tissue GABA is decreased in depression. Also, “in animal models, phenelzine, an inhibitor and substrate of monoamine oxidase (MAO), elevates cortical GABA levels” (Goldberg, Bell, & Pollard, 2014, p. 1). This long-held understanding that GABA levels are a factor in depression and the treatment of depression is the basis for the monoamine hypothesis of depression.
The medications that are effective on GABA levels enhance the short-term functions of the monoamines by inhibiting the functions of their transporters. Jeon and Kim (2016) of the International Journal of Molecular Sciences say that when selective serotonin reuptake inhibitors (SSRIs) were introduced, there was even more support for the hypothesis (Jeon & Kim, 2016, p. 3). However, when a patient with depressive symptoms begins treatment with an SSRI, there is a time lapse of 3 to 4 weeks before there is a response to the treatment, even though monoamine levels increase immediately. The monoamine receptor sensitivity hypothesis was created to address the limitation. This hypothesis says that the monoamines are secreted all the time and are increased by the treatment, which also activates the synapses to transmit, but the number of monoamine receptors are decreased due to the treatment also. “In other words, depression is induced by monoamine receptor up-regulation” (Jeon & Kim, 2016, p. 3). This hypothesis explains the 3 to 4 week time frame for treatment effects to begin, and it is usually the first choice for treatment of depression. ‘
These hypotheses are discussed here in a simplified way, but they are really quite groundbreaking. Mulinari (2012) of the Journal of the History of the Neurosciences explains that the hypotheses are a merger of data, concepts, standardized experimental techniques and animal models. The development of the antidepressants that arose from these hypotheses is also innovative because they affect the communication patterns between neurons in the brain that are facilitated by the neurotransmitters that the medications affect (Mulinari, 2012, p. 380). Mulinari (2012) also says that recent discoveries about antidepressant drugs are also revolutionary, “most importantly on the notion that TCAs block the uptake of monoamines from the intersynaptic space between neurons, and that MAOIs increase levels of available monoamines by inhibiting an enzyme that metabolizes monoamines” (Mulinari, 2012, p. 380). This then leads to the type of treatment that may be best for the patient who is experiencing depressive symptoms.
Pharmacological Intervention
One possible pharmacological intervention for this patient is an SSRI such as Zoloft. She has already been prescribed a low dose of Zoloft (usually 25 to 50 mg), but perhaps increasing the dose would be more effective. This can be done gradually, increasing the dose by 25 mg per week until she is taking 100 mg to 200 mg of Zoloft per day; however, it is not recommended to go over 200 mg per day. Yet, Zoloft is not the only possible pharmacological treatment for PPD.
A common treatment for PPD is an SSRI. If the patient were breastfeeding, an SSRI would not be a good option, but since she is not, it should be considered. Pawluski, Lonstein, and Fleming (2017) of Trends in Neurosciences explain that SSRIs may not be as effective on PPD as it is on other types of depression because “SSRIs may act on the maternal brain to reverse the behavioral effects of repeated stress by increasing synaptic density in the prefrontal cortex and the nucleus accumbens, and by increasing the number of immature neurons, but not synaptic plasticity, in the hippocampus. This suggests region-specific effects of SSRIs in the treatment of PPD” (Pawluski, Lonstein, & Fleming, 2017, pp. 12-13). However, there are still other options.
Another option is Brexanolone. Kanes, et al (2017) of Human Psychopharmacology: Clinical and Experimental explain that a metabolite of progesterone, allopregnanolone, increases during pregnancy reaching its highest levels during the third trimester. It declines quickly after childbirth, when the progesterone levels also decrease. “Allopregnanolone is a neuroactive steroid that has been shown in animal models to modulate neuronal excitability through direct action on synaptic and extrasynaptic GABAA receptors. It appears to play a significant role in affective disturbances that occur with changes in reproductive endocrine function, such as during the postpartum period” (Kanes, et al., 2017, pp. 1-2). The GABA receptors may not adapt as quickly as the decreases in these hormones which may be the cause of PPD. Kanes, et al (2017) say that starting an allopregnanolone equivalent in a dosage to the third trimester levels may be an effective pharmacological treatment. Kanes, et al. (2017) did an open-label, proof of concept study on Brexanolone with the objectives of evaluating safety and tolerability. They conclude, “This small exploratory study suggests that Brexanolone, and by extension positive allosteric GABAA receptor modulation with neuroactive steroids, may be an important therapeutic modality in PPD” (Kanes, et al., 2017, p. 4). However, some of the subjects in their study developed suicide ideation using this medication.
The patient may benefit from antidepressants called Serotonin Norepinephrine Reuptake Inhibitor (SNRIs) such as Venlafaxine (Effexor). Sansone and Sansone (2014) of Innovations in Clinical Neuroscience explain that serotonin norepinephrine reuptake inhibitors are in a family of antidepressants that inhibit the reuptake of both serotonin and norepinephrine. The drugs found in this group of antidepressants are similar, they have different chemical structures and different pharmacological properties (Sansone & Sansone, 2014, p. 37). Venlafaxine was the first SNRI to be marketed in the United States and has been approved by the United States Food and Drug Administration (FDA). Later, a different dosing formula of venlafaxine was introduced. There is less nausea and dizziness associated with the later formulation. Venlafaxine is a bicyclic and is structurally different from other SNRIs. The FDA has approved Venlafaxine for four clinical indications: major depression, generalized anxiety disorder, panic disorder, and social phobia. The half-life on the later formulation of venlafaxine (immediate release) is five hours. “The active metabolite of venlafaxine, o-desmethylvenlafaxine or desvenlafaxine, has a half-life of 11 hours. The XR formulation of venlafaxine demonstrates somewhat longer half-lives for both venlafaxine and desvenlafaxine at 11 hours and 13 to 14 hours, respectively” (Sansone & Sansone, 2014, p. 38). Venlafaxine is primarily metabolized through the liver which means it can cause drug interactions with many prescription medications and some common over-the-counter medications such as aspirin, ibuprofen, Nexium and Mucinex. It can also interact with vitamins B12, C, and D. Its side effects include headaches, nausea, fatigue and sexual dysfunction but higher doses may cause activation effects, dry mouth, and night sweats.
Venlafaxine has the dual action of both Serotonin Reuptake Inhibition (SRI) and Norepinephrine Reuptake Inhibition (NRI) if prescribed at doses greater than 150mg/day. A dose less than 150 mg per day provides only one action which is Serotonin Reuptake Inhibition (SRI). “Venlafaxine has a 30-fold higher affinity for the reuptake inhibition of serotonin compared to norepinephrine. In addition, venlafaxine inhibits serotonin and norepinephrine reuptake in a sequential manner, such that serotonin reuptake is initially inhibited, followed by norepinephrine reuptake inhibition” (Sansone & Sansone, 2014, p. 39). The patient’s father has also taken this medication for a lifelong treatment of depression, so that may indicate a genetic component to the PPD and to the treatment for it.
Other medications that can be added to the treatment regimen include Mirtazapine (Remeron) or Trazodone. Mirtazapine is a Serotonin Norepinephrine Disinhibitor (SNDI). Besides being an antidepressant, it also contains a histamine component to it when prescribed at a low dose between 7.5 mg to 15 mg/day. It is usually given at night to provide sedation to help patients sleep, and it is an appetite stimulant, which is good since the patient has lost weight quickly and now weighs less than before she became pregnant. When the patient reaches her ideal body weight, the medication can be discontinued and/or replaced with Trazodone. This medication is an antidepressant but it also used for sleep. It is usually prescribed at between 50 mg to 100 mg/day given at night prior to bedtime.
Nonpharmacological treatments may be tried along with pharmacological therapy for this patient. For instance, electroconvulsive therapy (ECT) or cognitive behavioral therapy (CBT) have been shown to be effective for PPD. Since she is suffering from a new onset depression, perhaps she could benefit from a milder form of non-pharmacological treatment. For example CBT, along with Venlafaxine and Mirtazapine may address the issues the patient is having and help her feel like herself again. Venlafaxine works well for her father, so it might be a good idea to discontinue the Zoloft and start her on Venlafaxine. The initial starting dose is 37.5 mg. After a week and if she tolerates that well, the dosage can be titrated up to 75 mg. If she tolerates the 75 mg for 2 weeks without any adverse effects, then it can be titrated up again to 150mg to be given twice daily. After another two weeks, if she tolerates the 150 mg without any adverse effects, the dose can be increased to 225 mg to be administered two to three times daily. The Mirtazapine will help her sleep and to gain weight, both of which will benefit this patient. The CBT will give her an opportunity to express her feelings and some strategies to cope with them also.
Patient Teaching Points
The patient should be told about the side effects of both Venlafaxine and Mirtazapine. Her EHR should be checked for possible drug interactions, and she should be told not to take common over-the-counter medications without first checking for interactions. She should be counseled on the frequency of dosing and the expected outcomes from the medications. She should also have CBT explained to her so she understands why it is included along with the pharmacological treatment.
Treatment Goals
The treatment goals for this patient include that she will self-report fewer depressive symptoms within 2 months of beginning the treatment with Venlafaxine and Mirtazapine using a Likert scale. For instance, the patient may say that she is feeling like her old self again. Another goal is for her to display evidenced-based outcome measures such as less weight loss, looking less disheveled, less fatigued, making better eye contact and less hesitation in her responses. Finally, another goal would be that the treatment’s side effects begin to diminish so that the patient can continue to be treated with the Venlafaxine without discomfort. If the depressive symptoms are genetic, she may need to continue the treatment indefinitely.
Conclusion
Hopefully the treatment with Venlafaxine and Mirtazapine will produce the desired treatment goals. If not, there are certainly other options that can be tried including returning to the Zoloft at higher doses. If PPD has a genetic component, it is possible that this is just the beginning of this patient living with depressive symptoms as her father has. However, it may also be just PPD, and the symptoms will eventually subside.
References
Goldberg, J. S., Bell, C. E., & Pollard, D. A. (2014). Revisiting the Monoamine Hypothesis of Depression: A New Perspective. Perspectives in Medicinal Chemistry, 6, 1-8. Retrieved from https://journals.sagepub.com/d...
Jeon, S. W., & Kim, Y.-K. (2016). Molecular Neurobiology and Promising New Treatment in Depression. International Journal of Molecular Sciences, 17, 1-17. doi:10.3390/ijms17030381
Kanes, S. J., Colquhoun, H., Doherty, J., Raines, S., Hoffmann, E., Rubinow, D. R., & Meltzer‐Brody, S. (2017).
Open‐label, proof‐of‐concept study of brexanolone in the treatment of severe postpartum depression. Human Psychopharmacology: Clinical and Experimental, 32(2), 1-6. Retrieved from https://onlinelibrary.wiley.co...
Mulinari, S. (2012). Monoamine Theories of Depression: Historical Impact on Biomedical Research. Journal of the History of the Neurosciences, 21, 366-392. Retrieved from http://content.ebscohost.com/C...
Pawluski, J., Lonstein, J., & Fleming, A. (2017). The Neurobiology of Postpartum Anxiety and Depression. Trends in Neurosciences, 40(2), 1-44. Retrieved from https://hal-univ-rennes1.archi...
Sansone, R. A., & Sansone, L. A. (2014). Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innovations in Clinical Neuroscience, 11(3-4), 37-42. Retrieved from https://www.ncbi.nlm.nih.gov/p...
